Breast cancer is the commonest cancer and leading cause of cancer death in women. Triple negative breast cancers are ER, PR and Her 2 Neu negative. These tumors have high propensity for metastatic spread. The lack of expression of ER, PR and Her 2 Neu receptors makes chemotherapy only option available to treat these aggressive tumors.
1) A study analyzed data from 687 patients with triple negative breast cancer who received surgery and adjuvant chemotherapy. The study found that as the time between surgery and starting chemotherapy increased, both 10-year disease-free survival and 10-year overall survival decreased.
2) Patients who started chemotherapy within 30 days of surgery had the best outcomes, with 10-year disease-free survival of 81.4% and 10-year overall survival of 82%.
3) Delaying the start of adjuvant chemotherapy by more than 90 days after surgery was associated with significantly worse survival outcomes.
This study compared short-course radiotherapy to long-course chemoradiation for patients with T3 rectal cancer. It found that long-course treatment resulted in a lower risk of local tumor recurrence, though the difference was not statistically significant. Both treatments had similar rates of distant tumor recurrence and overall survival. Long-course treatment seemed to provide a greater benefit for distal tumors, with fewer local recurrences, but again the difference was not statistically significant due to the small number of distal tumors.
This phase 3 study compared eribulin mesilate to treatment of physician's choice (TPC) in women with metastatic breast cancer who had received 2-5 prior chemotherapy regimens. 762 women were randomly assigned to eribulin (508 patients) or TPC (254 patients), which included chemotherapy, hormonal therapy, or symptomatic treatment. The primary endpoint was overall survival. Eribulin showed a significant improvement in median overall survival compared to TPC (13.1 months vs 10.6 months). The most common adverse events in both groups were fatigue and neutropenia. Peripheral neuropathy was the most common reason for discontinuing eribulin. This study demonstrates that eribulin provides a survival benefit compared
34320294 jak inhibitors more than just glucocorticoids (1)EVELIN LÁZARO
This editorial discusses recent trials investigating immunomodulatory therapies for COVID-19. It finds that treatment with glucocorticoids (dexamethasone) and JAK inhibitors reduces mortality in hospitalized patients receiving supplemental oxygen or ventilation. Combining JAK inhibitors with glucocorticoids may widen the window of benefit compared to either treatment alone. The editorial concludes that anti-inflammatory therapies reduce mortality in COVID-19 patients with moderate to severe disease, and that JAK inhibitors are a particularly promising option due to their oral administration, safety profile, and potential for combination with glucocorticoids.
1) Breast cancer is the most common malignancy among females worldwide. Survival rates vary significantly based on cancer stage, with metastatic breast cancer having only a 26% 5-year survival rate.
2) Hormonal therapy is first-line treatment for hormone receptor-positive metastatic breast cancer. Tamoxifen and aromatase inhibitors are commonly used, with aromatase inhibitors showing improved outcomes compared to tamoxifen. Fulvestrant and newer targeted agents are options for progressed disease.
3) Chemotherapy is also used to treat metastatic breast cancer. Commonly used agents include taxanes like paclitaxel and docetaxel, anthracyclines like doxorubicin, and newer options
Systemic Therapy in Breast Cancer.pptxAtulGupta369
Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy. Median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy. Olaparib and talazoparib are PARP inhibitors approved as monotherapies for deleterious/suspected deleterious germline BRCA-mutated, HER2-negative breast cancer.
1) A study analyzed data from 687 patients with triple negative breast cancer who received surgery and adjuvant chemotherapy. The study found that as the time between surgery and starting chemotherapy increased, both 10-year disease-free survival and 10-year overall survival decreased.
2) Patients who started chemotherapy within 30 days of surgery had the best outcomes, with 10-year disease-free survival of 81.4% and 10-year overall survival of 82%.
3) Delaying the start of adjuvant chemotherapy by more than 90 days after surgery was associated with significantly worse survival outcomes.
This study compared short-course radiotherapy to long-course chemoradiation for patients with T3 rectal cancer. It found that long-course treatment resulted in a lower risk of local tumor recurrence, though the difference was not statistically significant. Both treatments had similar rates of distant tumor recurrence and overall survival. Long-course treatment seemed to provide a greater benefit for distal tumors, with fewer local recurrences, but again the difference was not statistically significant due to the small number of distal tumors.
This phase 3 study compared eribulin mesilate to treatment of physician's choice (TPC) in women with metastatic breast cancer who had received 2-5 prior chemotherapy regimens. 762 women were randomly assigned to eribulin (508 patients) or TPC (254 patients), which included chemotherapy, hormonal therapy, or symptomatic treatment. The primary endpoint was overall survival. Eribulin showed a significant improvement in median overall survival compared to TPC (13.1 months vs 10.6 months). The most common adverse events in both groups were fatigue and neutropenia. Peripheral neuropathy was the most common reason for discontinuing eribulin. This study demonstrates that eribulin provides a survival benefit compared
34320294 jak inhibitors more than just glucocorticoids (1)EVELIN LÁZARO
This editorial discusses recent trials investigating immunomodulatory therapies for COVID-19. It finds that treatment with glucocorticoids (dexamethasone) and JAK inhibitors reduces mortality in hospitalized patients receiving supplemental oxygen or ventilation. Combining JAK inhibitors with glucocorticoids may widen the window of benefit compared to either treatment alone. The editorial concludes that anti-inflammatory therapies reduce mortality in COVID-19 patients with moderate to severe disease, and that JAK inhibitors are a particularly promising option due to their oral administration, safety profile, and potential for combination with glucocorticoids.
1) Breast cancer is the most common malignancy among females worldwide. Survival rates vary significantly based on cancer stage, with metastatic breast cancer having only a 26% 5-year survival rate.
2) Hormonal therapy is first-line treatment for hormone receptor-positive metastatic breast cancer. Tamoxifen and aromatase inhibitors are commonly used, with aromatase inhibitors showing improved outcomes compared to tamoxifen. Fulvestrant and newer targeted agents are options for progressed disease.
3) Chemotherapy is also used to treat metastatic breast cancer. Commonly used agents include taxanes like paclitaxel and docetaxel, anthracyclines like doxorubicin, and newer options
Systemic Therapy in Breast Cancer.pptxAtulGupta369
Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy. Median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy. Olaparib and talazoparib are PARP inhibitors approved as monotherapies for deleterious/suspected deleterious germline BRCA-mutated, HER2-negative breast cancer.
Safety and clinical activity of pembrolizumab for treatmentMarwa EL-Sayed
Pembrolizumab is a humanized monoclonal antibody that targets the PD-1 receptor. This study evaluated the safety and efficacy of pembrolizumab in 104 patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The results showed that pembrolizumab had a manageable safety profile, with 63% of patients experiencing drug-related adverse events mostly grade 1-2. Pembrolizumab also demonstrated promising anti-tumor activity with an 18% overall response rate. Progression-free survival was 13 months. This study provides evidence that pembrolizumab is a potential new treatment option for this patient population.
This study examined the association between breast cancer risk factors (such as parity, breastfeeding, age at menarche, family history, and BMI) and clinical outcomes (10-year mortality and 5-year recurrence rates) by molecular subtype, using data from 3012 women in Sarawak, Malaysia. The results showed that relationships between risk factors and outcomes varied by subtype. Specifically, among patients with the luminal A-like subtype, older age at menarche, underweight or overweight BMI were associated with worse prognosis, while parity/breastfeeding and older age at first full-term pregnancy were associated with better prognosis. Adding these risk factors improved prognostic prediction for luminal A-like patients beyond standard clinicopathological factors alone.
Docetaxel Versus Docetaxel/Cisplatin in NSCLCJames Hilbert
This study compared docetaxel alone versus docetaxel plus cisplatin as frontline treatment for advanced non-small cell lung cancer. 302 patients were randomly assigned to receive either docetaxel alone (146 patients) or the docetaxel/cisplatin combination (156 patients). The overall response rate was significantly higher for the combination at 36% versus 18% for docetaxel alone. However, median survival time, time to disease progression, and 1-year survival rates were similar between the two groups. Toxicity was higher with the combination therapy. Both regimens showed similar effectiveness in terms of survival, though the combination resulted in a higher response rate and more toxicity.
Treatment of Ovarian Cancer First Line Chemotherapy or Targeted Therapy for R...ijtsrd
Ovarian cancer is the seventh most common gynecological cancer worldwide, ovarian cancer is the eighth leading cause of cancer death in women. In recent years, the number of ovarian cancer cases has been increasing in Japan, more than 9,000 women are diagnosed with ovarian cancer each year. The 5 year survival rate is 58 , the lowest among gynecological cancers, 4,758 ovarian cancer deaths in 2012. That is, it is reported that about one in two ovarian cancer patients has died. Because it is difficult to cure recurrent ovarian cancer, treatment is used to prolong life and improve quality of life. Because PARP inhibitors are oral targeted drugs that specifically act on cancer cells, they are expected to reduce the risk of disease progression and death while maintaining a good safety profile. In this way, the development of oral preparations has made it possible to avoid the burden on patients such as pain caused by conventional injections and the time constraints required for infusion. In this review, we discuss new treatments for ovarian cancer. Takuma Hayashi | Kaoru Abiko | Ken Yamaguchi | Junzo Hamanishi | Masaki Mandan | Ikuo Konishi "Treatment of Ovarian Cancer: First-Line Chemotherapy or Targeted Therapy for Recurrent Cases" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-4 | Issue-3 , April 2020, URL: https://www.ijtsrd.com/papers/ijtsrd30470.pdf Paper Url :https://www.ijtsrd.com/medicine/other/30470/treatment-of-ovarian-cancer-firstline-chemotherapy-or-targeted-therapy-for-recurrent-cases/takuma-hayashi
This document describes a study protocol for a randomized phase III clinical trial comparing neoadjuvant chemoradiation followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell carcinoma of the esophagus. The trial aims to enroll 350 patients total with 175 patients in each arm. The primary objective is to compare median survival rates and quality of life between the two treatment groups. Secondary objectives include comparing pathological responses, progression-free survival, number of complete resections, treatment toxicity, and costs. The chemoradiation regimen involves weekly paclitaxel and carboplatin chemotherapy with concurrent radiation over 5 weeks. Patients will then undergo surgery and be followed up for survival and quality of life outcomes
1. The document discusses the standard treatment for locally advanced cervical cancer, which is concurrent chemoradiotherapy with cisplatin. Several randomized trials from the 1990s showed improved survival with this approach compared to radiotherapy alone.
2. Meta-analyses of these trials demonstrated a 6-8% absolute improvement in survival at 5 years with the addition of chemotherapy to radiotherapy. Cisplatin is the recognized cytotoxic drug used most commonly.
3. The study described in the document investigated the use of ifosfamide and cisplatin with concurrent chemoradiotherapy and consolidation chemotherapy as a potentially improved treatment approach for locally advanced cervical cancer.
The Potential for Individualization of Neoadjuvant Chemotherapy in Breast Can...CrimsonpublishersCancer
The preoperative, or, as it is often called, neoadjuvant chemotherapy (NAPCT) of operable breast cancer (the breast cancer) with affected regional lymph nodes has in its time replaced preoperative radiotherapy, as it has a number of significant advantages over the latter. The most important advantage of NAPCT is its systemic action, which allows to “catching up” with probable distant micro-metastases or circulating tumor cells, while pre-operative radiotherapy has a local effect, and on the systemic level the tumor continues to develop. Despite of the fact that with operative breast cancer the time of NAPCT (before or after the operation) does not affect to the long-term results of treatment, the latter becomes applicable even for operable breast cancer without affected regional lymph nodes.According to the literature, NAPCT with primary-operative breast cancer allows: 1) make organ saving operations; 2) improve the prognosis in cases of complete morphological regression in patients with triple negative and Her2 / neu positive (non-luminal) subtypes; 3) evaluate the effect of chemotherapy and, in the absence of effect, stop it on time [1].
The study evaluated dual HER2 blockade with lapatinib plus trastuzumab plus an aromatase inhibitor compared to trastuzumab plus an aromatase inhibitor or lapatinib plus an aromatase inhibitor in patients with HER2-positive, hormone receptor-positive metastatic breast cancer. 355 patients were randomly assigned to one of the three treatment arms. The results showed that progression-free survival was significantly longer in the lapatinib plus trastuzumab plus aromatase inhibitor arm compared to the trastuzumab plus aromatase inhibitor arm, with overall response and clinical benefit rates also being higher. Overall survival data were immature but trended in favor of the lapatinib plus trastuzumab arm. The most common
1) The document discusses antibody-drug conjugates (ADCs) for the treatment of HER2-positive breast cancer, including FDA-approved ADCs Kadcyla (ado-trastuzumab emtansine), Enhertu (fam-trastuzumab deruxtecan), and Trodelvy (sacituzumab govitecan).
2) Clinical trial results showed that adding pertuzumab or neratinib to standard chemotherapy and trastuzumab improved outcomes for patients with early-stage HER2-positive breast cancer.
3) The KATHERINE trial found that for patients with residual disease after neoadjuvant therapy, T-DM1 led
1. The study analyzed treatment patterns over time in patients receiving first-line chemotherapy for advanced or metastatic esophageal or gastric cancer based on data from 2,808 patients documented in Therapiemonitor from 2006-2013.
2. Treatment intensity increased over time, with 49.3% of patients receiving triplet chemotherapy in 2013 compared to just 10.1% in 2006. HER2 testing rates increased from 49.1% in earlier studies to 79.1% in 2012-2013, though testing was still not always performed according to guidelines.
3. Usage of fluoropyrimidine/cisplatin combinations with trastuzumab declined from 67% in 2010-2011 to 50% in 2012-2013
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdfDoriaFang
What are the new anti-cancer drugs approved in the first half of the year? The new drugs approved covered a variety of solid tumors and blood tumor types.
Mechanisms of resistance to trastuzumab emtansine (t dm1) in her2-positive br...nataly bedoya
T-DM1 is an antibody-drug conjugate approved for HER2-positive breast cancer. It has multiple mechanisms of action including HER2 signaling blockade, immune-mediated cell killing, and microtubule poisoning from its DM1 payload. The review summarizes clinical trials showing T-DM1's efficacy. It also outlines various proposed resistance mechanisms relating to each of T-DM1's mechanisms. Based on experimental data, the resistance mechanisms most strongly supported involve dysfunctional intracellular metabolism of T-DM1 and evasion of DM1-mediated cell killing. Loss of HER2 dependence and impacts of other factors like EGFR require more investigation. Understanding resistance can help develop strategies to overcome it, like new ADCs.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...NainaAnon
1. The study found that IRF5 was upregulated in hepatocellular carcinoma (HCC) tissues compared to normal tissues based on mRNA and protein levels.
2. Overexpression of IRF5 promoted the growth and colony formation of HCC cells in vitro, while silencing IRF5 inhibited HCC cell growth and proliferation.
3. TRIM35 was found to interact with and promote the degradation of IRF5. TRIM35 expression was negatively correlated with IRF5 levels in HCC clinical samples.
Trimodal Management of Locally Invasive Urinary Bladder CancerNainaAnon
To evaluate the response of the modern bladder-preservation treatment modality; Trimodal Therapy (TMT) in Muscle-Invasive Bladder Cancer (MIBC). Aiming at bladder preservation in MIBC, TMT was to offer a quality- of-life advantage and avoid potential morbidity and mortality of Radical Cystectomy (RC) without compromising oncologic outcomes.
Alterations of Gut Microbiota From Colorectal Adenoma to CarcinomaNainaAnon
The document analyzes differences in gut microbiota between healthy individuals, those with colorectal adenomas (CRA), and those with colorectal cancer (CRC). 16S rRNA sequencing was performed on tissue samples from 11 individuals in each group. Microbial diversity was lower in CRA patients and higher in CRC patients compared to healthy individuals. The relative abundance of Fusobacteria was lower in CRA and higher in CRC. This suggests alterations in gut microbiota occur from adenoma to carcinoma, with Fusobacteria potentially playing a role in colorectal cancer development.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...NainaAnon
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Uretero-Enteric Anastomosis Stricture after Urinary Diversion; Detailed Analy...NainaAnon
To report the lessons we have learned in the management of uretero-enteric anastomosis stricture (UEAS) in a tertiary urology center over a decade of experience.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...NainaAnon
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Safety and clinical activity of pembrolizumab for treatmentMarwa EL-Sayed
Pembrolizumab is a humanized monoclonal antibody that targets the PD-1 receptor. This study evaluated the safety and efficacy of pembrolizumab in 104 patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The results showed that pembrolizumab had a manageable safety profile, with 63% of patients experiencing drug-related adverse events mostly grade 1-2. Pembrolizumab also demonstrated promising anti-tumor activity with an 18% overall response rate. Progression-free survival was 13 months. This study provides evidence that pembrolizumab is a potential new treatment option for this patient population.
This study examined the association between breast cancer risk factors (such as parity, breastfeeding, age at menarche, family history, and BMI) and clinical outcomes (10-year mortality and 5-year recurrence rates) by molecular subtype, using data from 3012 women in Sarawak, Malaysia. The results showed that relationships between risk factors and outcomes varied by subtype. Specifically, among patients with the luminal A-like subtype, older age at menarche, underweight or overweight BMI were associated with worse prognosis, while parity/breastfeeding and older age at first full-term pregnancy were associated with better prognosis. Adding these risk factors improved prognostic prediction for luminal A-like patients beyond standard clinicopathological factors alone.
Docetaxel Versus Docetaxel/Cisplatin in NSCLCJames Hilbert
This study compared docetaxel alone versus docetaxel plus cisplatin as frontline treatment for advanced non-small cell lung cancer. 302 patients were randomly assigned to receive either docetaxel alone (146 patients) or the docetaxel/cisplatin combination (156 patients). The overall response rate was significantly higher for the combination at 36% versus 18% for docetaxel alone. However, median survival time, time to disease progression, and 1-year survival rates were similar between the two groups. Toxicity was higher with the combination therapy. Both regimens showed similar effectiveness in terms of survival, though the combination resulted in a higher response rate and more toxicity.
Treatment of Ovarian Cancer First Line Chemotherapy or Targeted Therapy for R...ijtsrd
Ovarian cancer is the seventh most common gynecological cancer worldwide, ovarian cancer is the eighth leading cause of cancer death in women. In recent years, the number of ovarian cancer cases has been increasing in Japan, more than 9,000 women are diagnosed with ovarian cancer each year. The 5 year survival rate is 58 , the lowest among gynecological cancers, 4,758 ovarian cancer deaths in 2012. That is, it is reported that about one in two ovarian cancer patients has died. Because it is difficult to cure recurrent ovarian cancer, treatment is used to prolong life and improve quality of life. Because PARP inhibitors are oral targeted drugs that specifically act on cancer cells, they are expected to reduce the risk of disease progression and death while maintaining a good safety profile. In this way, the development of oral preparations has made it possible to avoid the burden on patients such as pain caused by conventional injections and the time constraints required for infusion. In this review, we discuss new treatments for ovarian cancer. Takuma Hayashi | Kaoru Abiko | Ken Yamaguchi | Junzo Hamanishi | Masaki Mandan | Ikuo Konishi "Treatment of Ovarian Cancer: First-Line Chemotherapy or Targeted Therapy for Recurrent Cases" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-4 | Issue-3 , April 2020, URL: https://www.ijtsrd.com/papers/ijtsrd30470.pdf Paper Url :https://www.ijtsrd.com/medicine/other/30470/treatment-of-ovarian-cancer-firstline-chemotherapy-or-targeted-therapy-for-recurrent-cases/takuma-hayashi
This document describes a study protocol for a randomized phase III clinical trial comparing neoadjuvant chemoradiation followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell carcinoma of the esophagus. The trial aims to enroll 350 patients total with 175 patients in each arm. The primary objective is to compare median survival rates and quality of life between the two treatment groups. Secondary objectives include comparing pathological responses, progression-free survival, number of complete resections, treatment toxicity, and costs. The chemoradiation regimen involves weekly paclitaxel and carboplatin chemotherapy with concurrent radiation over 5 weeks. Patients will then undergo surgery and be followed up for survival and quality of life outcomes
1. The document discusses the standard treatment for locally advanced cervical cancer, which is concurrent chemoradiotherapy with cisplatin. Several randomized trials from the 1990s showed improved survival with this approach compared to radiotherapy alone.
2. Meta-analyses of these trials demonstrated a 6-8% absolute improvement in survival at 5 years with the addition of chemotherapy to radiotherapy. Cisplatin is the recognized cytotoxic drug used most commonly.
3. The study described in the document investigated the use of ifosfamide and cisplatin with concurrent chemoradiotherapy and consolidation chemotherapy as a potentially improved treatment approach for locally advanced cervical cancer.
The Potential for Individualization of Neoadjuvant Chemotherapy in Breast Can...CrimsonpublishersCancer
The preoperative, or, as it is often called, neoadjuvant chemotherapy (NAPCT) of operable breast cancer (the breast cancer) with affected regional lymph nodes has in its time replaced preoperative radiotherapy, as it has a number of significant advantages over the latter. The most important advantage of NAPCT is its systemic action, which allows to “catching up” with probable distant micro-metastases or circulating tumor cells, while pre-operative radiotherapy has a local effect, and on the systemic level the tumor continues to develop. Despite of the fact that with operative breast cancer the time of NAPCT (before or after the operation) does not affect to the long-term results of treatment, the latter becomes applicable even for operable breast cancer without affected regional lymph nodes.According to the literature, NAPCT with primary-operative breast cancer allows: 1) make organ saving operations; 2) improve the prognosis in cases of complete morphological regression in patients with triple negative and Her2 / neu positive (non-luminal) subtypes; 3) evaluate the effect of chemotherapy and, in the absence of effect, stop it on time [1].
The study evaluated dual HER2 blockade with lapatinib plus trastuzumab plus an aromatase inhibitor compared to trastuzumab plus an aromatase inhibitor or lapatinib plus an aromatase inhibitor in patients with HER2-positive, hormone receptor-positive metastatic breast cancer. 355 patients were randomly assigned to one of the three treatment arms. The results showed that progression-free survival was significantly longer in the lapatinib plus trastuzumab plus aromatase inhibitor arm compared to the trastuzumab plus aromatase inhibitor arm, with overall response and clinical benefit rates also being higher. Overall survival data were immature but trended in favor of the lapatinib plus trastuzumab arm. The most common
1) The document discusses antibody-drug conjugates (ADCs) for the treatment of HER2-positive breast cancer, including FDA-approved ADCs Kadcyla (ado-trastuzumab emtansine), Enhertu (fam-trastuzumab deruxtecan), and Trodelvy (sacituzumab govitecan).
2) Clinical trial results showed that adding pertuzumab or neratinib to standard chemotherapy and trastuzumab improved outcomes for patients with early-stage HER2-positive breast cancer.
3) The KATHERINE trial found that for patients with residual disease after neoadjuvant therapy, T-DM1 led
1. The study analyzed treatment patterns over time in patients receiving first-line chemotherapy for advanced or metastatic esophageal or gastric cancer based on data from 2,808 patients documented in Therapiemonitor from 2006-2013.
2. Treatment intensity increased over time, with 49.3% of patients receiving triplet chemotherapy in 2013 compared to just 10.1% in 2006. HER2 testing rates increased from 49.1% in earlier studies to 79.1% in 2012-2013, though testing was still not always performed according to guidelines.
3. Usage of fluoropyrimidine/cisplatin combinations with trastuzumab declined from 67% in 2010-2011 to 50% in 2012-2013
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdfDoriaFang
What are the new anti-cancer drugs approved in the first half of the year? The new drugs approved covered a variety of solid tumors and blood tumor types.
Mechanisms of resistance to trastuzumab emtansine (t dm1) in her2-positive br...nataly bedoya
T-DM1 is an antibody-drug conjugate approved for HER2-positive breast cancer. It has multiple mechanisms of action including HER2 signaling blockade, immune-mediated cell killing, and microtubule poisoning from its DM1 payload. The review summarizes clinical trials showing T-DM1's efficacy. It also outlines various proposed resistance mechanisms relating to each of T-DM1's mechanisms. Based on experimental data, the resistance mechanisms most strongly supported involve dysfunctional intracellular metabolism of T-DM1 and evasion of DM1-mediated cell killing. Loss of HER2 dependence and impacts of other factors like EGFR require more investigation. Understanding resistance can help develop strategies to overcome it, like new ADCs.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...NainaAnon
1. The study found that IRF5 was upregulated in hepatocellular carcinoma (HCC) tissues compared to normal tissues based on mRNA and protein levels.
2. Overexpression of IRF5 promoted the growth and colony formation of HCC cells in vitro, while silencing IRF5 inhibited HCC cell growth and proliferation.
3. TRIM35 was found to interact with and promote the degradation of IRF5. TRIM35 expression was negatively correlated with IRF5 levels in HCC clinical samples.
Trimodal Management of Locally Invasive Urinary Bladder CancerNainaAnon
To evaluate the response of the modern bladder-preservation treatment modality; Trimodal Therapy (TMT) in Muscle-Invasive Bladder Cancer (MIBC). Aiming at bladder preservation in MIBC, TMT was to offer a quality- of-life advantage and avoid potential morbidity and mortality of Radical Cystectomy (RC) without compromising oncologic outcomes.
Alterations of Gut Microbiota From Colorectal Adenoma to CarcinomaNainaAnon
The document analyzes differences in gut microbiota between healthy individuals, those with colorectal adenomas (CRA), and those with colorectal cancer (CRC). 16S rRNA sequencing was performed on tissue samples from 11 individuals in each group. Microbial diversity was lower in CRA patients and higher in CRC patients compared to healthy individuals. The relative abundance of Fusobacteria was lower in CRA and higher in CRC. This suggests alterations in gut microbiota occur from adenoma to carcinoma, with Fusobacteria potentially playing a role in colorectal cancer development.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...NainaAnon
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Uretero-Enteric Anastomosis Stricture after Urinary Diversion; Detailed Analy...NainaAnon
To report the lessons we have learned in the management of uretero-enteric anastomosis stricture (UEAS) in a tertiary urology center over a decade of experience.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...NainaAnon
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Combined Analysis of Micro RNA and Proteomic Profiles and Interactions in Pat...NainaAnon
The Liquid Mass System(LMS) includes an Easy nLC1000 (Thermo Fisher) coupled ultra-high resolution mass spectrometer Orbitrap Fusion Lumos (Thermo Fisher) with a Thermo Fisher electrospray source. Each injection is sent to a preset column (Acclaim PepMap C18, 100 μm x 2 cm, Thermo Scientific) for adsorption at a flow rate of 3 L/min. The sample is then sent to the analyzer column (Acclaim PepMap C18, 75 μm x 15 cm, Thermo Scientific) for separation
Skeletal muscle channelopathy are rare heterogeneous episodic disorders with marked genotypic and phenotypic variability resulting in periodic paralysis, and falls in young people which often misdiagnosed or undiagnosed due to its rarity, often the symptoms are miscommunicated to the treating phycision due to its episodic nature and not uncommonly physical examination by the time patient attend the clinic or hospital will be unremarkable apart from periodic muscle paralysis where patient will presented to ED with flaccid weakness,
The Use of the Infrared Laser Therapy of 890-910 NM for the Treatment Breast ...NainaAnon
The document summarizes experimental and clinical research on using infrared laser therapy between 890-910 nm to treat breast cancer. Experimental studies showed laser therapy inhibited tumor growth in mice and rats, with the most effective dose being 0.46 J/cm2. Clinical studies involved 136 patients with breast cancer divided into 3 groups: those receiving laser therapy before surgery, after surgery, or as the sole treatment. Laser therapy reduced postoperative complications, improved immune function and quality of life, and increased survival time. Histological analysis found over 50% of tumor tissue disappeared due to necrosis and fibrosis with effective laser treatment regimens.
The Use of the Infrared Laser Therapy of 890-910 NM for the Treatment Breast ...NainaAnon
The experimental studies were conducted with Walker's carcinosarcoma n256 (from the U.S.A. bank), cancer of the mammary gland (RMK-1). Spontaneous –mice with mammary glands cancer (type B). The tasks were as follows: to study the effect of different doses LLLT on the growth of experimental tumors. Evaluation of the effectiveness by applying LLLT in combination with various chemotherapeutic agents (vincristin, 5-Fu, ciclophosphan). Research of LLLR effect on different types of tumors show that this treatment can be used for tumors-statistic effect and for increasing life-span in animals. Applying LLLR in combination with chemotherapeutic agents causes tumors-static action. The most effective combination was LLLT + vincristin which caused the inhibition of tumor growth in Walker's carcinosarcoma-by 92,87%, in RMK-1 - by 90,29% in comparing to controls. The combination of LLLT with HpD showed - the effect of laser therapy takes place in 30 min before the irradiation and is accompanied by a sharp reduction of the preparation's accumulation in the tumor cells.
Prevalence of Hpv Infection in the Lekoumou and Niari Departments (Congo Braz...NainaAnon
This study aimed to determine the prevalence of HPV infection in women in the Lekoumou and Niari departments of Congo Brazzaville. The researchers collected samples from 100 women aged 16-73 and tested them for HPV. They found an overall HPV prevalence of 29%, with the highest rates (58.3%) in women over 50. No significant associations were found between HPV infection and factors like education level, age of first intercourse, number of sexual partners, or number of pregnancies. The study provides baseline data on HPV prevalence in these regions of Congo to help guide cervical cancer prevention efforts.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...NainaAnon
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Follow-Up Strategies in Focal Liver Lesions And Treatment MethodsNainaAnon
Today, advances in cross-sectional imaging have led to the detection and early recognition of incidental/focal liver lesions (FCL). In approximately 17,000 cases of chest CT, incidental liver lesions were found in 6% [1]. In general, FCL consists of hepatocytes, biliary epithelium, mesenchymal tissue, connective tissue, or metastasized cells from distant sites. Most incidental lesions are benign, some may require careful management and treatment.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...NainaAnon
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Predictive Value of Biomarkers Fibrinogen Like Protein-2 and A-Fetoprotein fo...NainaAnon
Data concerning the utility of biomarkers for accurate early HCC detection in cirrhotic patients are lacking. 1.2. Methods: We evaluated 112 consecutive Caucasian cirrhotic patients with (n=28) or without (n=84) concomitant HCC at baseline for serum AFP and plasma fibrinogen like protein-2 (FGL-2) levels. Patients without confirmed HCC at baseline were further followed up every six months with ultrasound and serum AFP levels, according to HCC surveillance program. Imaging as well as histological confirmation of HCC was established in patients with new lesions. Du
The Black Fungus is One of the Bad Consequences of COVID 19NainaAnon
Recently, since the emergence of the Covid 19 pandemic, the whole world has been waiting for what comes after Corona and when that pandemic will disappear and how to get rid of it. Therefore, all countries, whether Arab or foreign, sought to empty scientific research to produce a vaccine to treat this pandemic. These circumstances have inflicted material and human losses for all countries. In an attempt to combat Covid 19 after the vaccine was manufactured, however, the winds are coming in what ships do not desire, so there is a new outbreak, namely the black fungus.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...NainaAnon
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Research Progress in Chronic Lymphocytic LeukemiaNainaAnon
Cancer is an uncontrolled division of cell occurs due to genetic alterations and mutation. Chronic lymphocytic leukemia is the heterogeneous lymphocytic malignancy worldwide that leads to death. The advancement of genetic analysis techniques and the identification of suitable biomarkers show significant differences in the treatment period. In this paper will discuss the microRNA that is small Non-coding RNAs and is involved in CLL beginning, development, and resistance to therapy and also will explain the stages of CLL.
Genetics of Breast and Ovary Cancers Associated with Hereditary Cancers and t...NainaAnon
Carriers of the BRCA-1/2 mutation have increased and variable risks of Breast Cancer (BC) and ovarian cancer and vary or are modified by common genetic variants and their incidence genetic testing and risk-reducing surgery has increased, they should receive advice and evaluation by the physician with experience in genetics.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler Community Health Nursing A Canadian Perspective, 5th Edition TEST BANK by Stamler Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Study Guide Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Studocu Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Course Hero Community Health Nursing A Canadian Perspective, 5th Edition Answers Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Course hero Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Studocu Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Study Guide Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Ebook Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Questions Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Studocu Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Stuvia
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
1. Selecting Optimal Regimen in The treatment of Metastatic Tri-
ple Negative Breast Cancer
Mehmood S, Mahmood H and Faheem M
Department of Oncology, Nuclear Medicine, Oncology and Radiotherapy Institute (NORI) Islamabad, Pakistan
Volume 1 Issue 4- 2018
Received Date: 21 June 2018
Accepted Date: 20 July 2018
Published Date: 29 July 2018
1. Abstract
Breast cancer is the commonest cancer and leading cause of cancer death in women. Triple
negative breast cancers are ER, PR and Her 2 Neu negative. These tumors have high propensity
for metastatic spread. The lack of expression of ER, PR and Her 2 Neu receptors makes chemo-
therapy only option available to treat these aggressive tumors. This study examines various clini-
cal trials that will help clinicians in selecting appropriate drugs for the treatment of this subset
of patients.
Clinics of Oncology
Citation: Mehmood S, Mahmood H and Faheem M, Selecting Optimal Regimen in The treatment of Meta-
static Triple Negative Breast Cancer. Clinics of Oncology. 2018; 1(4): 1-8.
United Prime Publications: http://unitedprimepub.com
3. Introduction
Breast Cancer is the commonest cancer and leading cause of can-
cer death in women. In the year 2012 approximately 1,671,149
new patients were diagnosed with breast cancer and 521,907
deaths were attributed to this menace [1]. According to SEER
Cancer Registry 95% of the patients have localized disease at
initial presentation whereas 5% of patients present with meta-
static disease [2]. About 20-30% of early stage patients develop
systemic disease at some point in life [3]. In Pakistan every year
approximately 90,000 women are diagnosed with breast cancer
and most of these patients have either locally advanced or meta-
static disease [4]. A study conducted by Gilani et al. [5] showed
that 25-36% of Pakistani women present with disseminated dis-
ease.
The prognosis of patients with metastatic breast cancer is ex-
tremely poor. Despite recent advances and advent of novel ther-
apies, the disease remains incurable with mean survival of 31.8
months [6].
Breast cancer generally comprises of 4 subgroups: ER PR posi-
tive Her 2 Neu negative; ER PR Her2 Neu positive; ER PR nega-
tive Her 2 Neu positive and ER PR Her 2 Neu negative.
Triple negative phenotype also known as Basal breast tumors
are hormone receptors i.e. ER and PR and Her 2 Neu negative.
Different subtypes of TNBC have been lately recognized using
gene expression (GE) analysis. These subtypes include BL1 with
cell cycle and DNA damage response GE signatures, BL2 with
*Corresponding Author (s): Humera Mahmood, Department of Oncology, Nuclear
Medicine, Oncology and Radiotherapy Institute (NORI) Islamabad, Pakistan, E-mail:
hmhfaheem02@gmail.com
Review Article
growth factor signaling and myoepithelial markers, two mes-
enchymal subtypes M and MSL with high expression of genes
involved in differentiation and growth factor pathways, Immu-
nomodulatory type and luminal subtype characterized by an-
drogen signaling [7].
Triple negative breast tumors have worst prognosis and are char-
acterized by an aggressive disease course and propensity for vis-
ceral metastasis leading to reduction in Disease Free Survival
and Overall Survival [8]. The median OS in patients with meta-
static triple negative tumors is just 13.3 months [9].
The lack of expression of hormone receptors and Her 2 Neu
makes chemotherapy only option available to date for the treat-
ment of these aggressive metastatic tumors. The aim of this arti-
cle is to review existing chemotherapy regimens and help clini-
cans in selecting appropriate chemotherapeutic drugs for the
treatment of this subset of patients Table 1. The choice of single
agent over combination chemotherapy in metastatic breast can-
cer depends on age, performance status, rate of tumor progres-
sion and disease burden. In patients who are elderly, have poor
performance status and have slowly growing tumors, single agent
chemotherapy is chosen where as in those having large tumor
burden or rapidly progressing disease, combination chemother-
apy is the preferred treatment modality [10]. A meta-analysis
was conducted by Dear et al. [11] in 2013 comparing sequential
single agent vs. combination chemotherapy in metastatic cancer.
The authors concluded that there was a greater risk of progres-
sion in combination arm compared to sequential single agent
arm (HR 1.16; 95% CI 1.03 to 1.31; P = 0.01), higher response
2. Keywords
Triple negative; Breast cancer;
Metastasis
3. ment though not statistically significant favoured nab paclitaxel
(6.2 vs. 5.4 months).
2. Soria JC, Ohe Y, Vansteenkiste J. Osimertinib in Untreated EGFR-
Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;
378(2): 113-125.
Author
Trial
Phase
Treatment Regi-
men
PFS OS RR
Tannock et al34
Phase III
High dose vs.
conventional
dose
CMF
-
15.6 vs.
12.8
months
30% vs.
11%
Lopez et al36
Phase III FAC vs. FEC similar similar
46% vs.
44%
Katsumata et
al37
Phase III
AC vs. Docetaxel
vs. AC-T
6.4, 6.4,
6.7
months
22.6, 25.7
and 25
months
30%,
41%,
35%
Biganzoli et al38
Phase III AT vs. AC 6 months
20.6 vs.
20.5
months
54% vs.
58%
Bontenbal
et al39
Phase III AT vs. FAC
8 vs. 6.6
months
22.6 vs.
16.2
months
58% vs.
37%
O’Shaughnessy
et al42
Phase III
Capecitabine
Docetaxel vs.
Docetaxel alone
6.1 vs. 4.2
months
14.5 vs.
11.5
monthes
42% vs.
30%
Fan et al45
Phase III
Docetaxel Cispl-
atin vs.
Docetaxel
Capecitabine
10.9 vs.
4.8
months
32.8
months
versus 21.5
63% vs.
15.4%
Thomas et al46
Phase III
Ixabepilone
capecitabine vs.
capecitabine
alone
5.8 vs. 4.2
months
_
35% vs.
14%
Hu et al48
Phase III
Cisplatin Gemcit-
abine vs.
Gemcitabine
paclitaxel
7.73 vs.
6.47
months
_ _
Yardley et al49
Phase
II/III
nab paclitaxel+
carboplatin or
gemcitabine vs.
gemcitabine
carboplatin
7.4, 5.4, 6
months
_ _
Farhat et al50
Phase II
Lipoplatin +
vinorelbine
8 months 21 months 53.10%
Table 2: Summarizes progression free survival, overall survival and response
rates of various chemotherapeutic agents used in different combinations in
the treatment of metastatic triple negative breast cancer.
4.3. Capecitabine
It can be used as either first, second or third line in the manage-
ment of disseminated breast cancer. Kotsori et al. [20] retrospec-
tively analyzed 89 patients with metastatic triple negative breast
cancer. Capecitabine was given as first line in 53% and as second
or third line in 47% patients. An overall response rate of around
21%, median progression free survival of 11 weeks and overall
survival of 39 weeks was seen. There was no difference in efficacy
when used as either line.
Capecitabine when used as first line is as efficacious as paclitaxel.
Talbot et al compared paclitaxel with capecitabine in patients
with prior anthracycline exposure. An overall response rate of
36% was seen in capecitabine group and 26% in paclitaxel group.
Median progression free survival (3.0 vs. 3.1 months) and overall
survival (7.6 vs. 9.4 months) were comparable in both groups
[21].
This chemotherapeutic agent is preferred in elderly patients due
to better tolerability. Dose reduction in such patients from 1250
mg/m2 PO B.D to 1000 mg/m2 decreases the toxicity without
effecting on efficacy [22].
Capecitabine achieved equivalent results when compared with
liposomal doxorubicin. PELICAN trial was the first trial to com-
pare capecitabine and liposomal doxorubicin in terms of efficacy
and toxicity. The results of this trial have been recently published.
An overall response rate of 10.7 and 12.9 % was seen in liposomal
doxorubicin and capecitabine arm respectively. Median overall
survival was 23.3 months in liposomal doxorubicin and 26.8
months in capecitabine arm. Median progression free survival
was similar i.e. 6 months in both groups [23].
Gemcit binIt is not commonly used as single agent in the man-
agement of metastatic breast cancer. In heavily treated metastatic
breast cancer patients, Rha et al. [24] studied the role of gemcit-
abine monotherapy as salvage regimen. An overall response rate
of 20% was seen with two complete responses. The median re-
sponse duration was 9 months whereas median overall survival
was 12 months when used as third line and 7 months when used
as fourth line chemotherapy.
Gemcitabine is inferior to epirubicin when used as first line in
the treatment of metastatic breast cancer. Results of phase III
trial comparing gemcitabine and epirubicin revealed superior
response rates (40.3 vs 16.4 % p <0.001), better progression free
survival (6.1 vs. 3.4 months p=0.0001) and improved overall sur-
vival (19.1 vs. 11.8 months p=0.0004) for epirubicin [25].
4.4. Vinorelbine
It is a vinca alkaloid used as salvage chemotherapy after failure
of anthracyclines and taxanes in patients with metastatic breast
cancer. An overall response rate of 25% with median time to tu-
mor progression and overall survival of 6 months is achieved in
this setting [26].
Vinorelbine due to its better toxicity profile can be given as first
line in elderly patients in whom anthracyclines and taxanes are
contraindicated. Vogel et al conducted a multicenter phase II
trial in women aged 60 years or older
with advanced breast cancer. The objective response rate was
38% and median progression free survival was 6 months [27].
4.5. Platinums (Cisplatin/Carboplatin)
A number of studies with conflicting results have been carried
out evaluating the role of platinums in metastatic triple negative
breast cancer.
Volume 1 Issue 4-2018 Review Article
United Prime Publications: http://unitedprimepub.com 3
4. TBCRC009 was a multicenter phase II clinical trial in which
metastatic triple negative breast cancer patients were enrolled
to receive either cisplatin or carboplatin depending on physi-
cians’ choice. Overall response rate was 25.6% and was superior
with cisplatin compared with carboplatin (32.6 vs. 18.7%). RR of
54.5% was seen in patients with BRCA1/2 mutations. In patients
without germline BRCA 1/2 mutations BRCA-like genomic in-
stability signature distinguished responding and nonresponding
cases. Median PFS was 89 days but in those who responded well
to treatment median PFS was 242 days. Platinums were associ-
ated with a response rate of 33% and 17% when used as first line
and second line respectively [28].
TNT trial revealed no benefit of carboplatin over docetaxel in
patients with triple negative breast cancer. However subgroup
analyses suggested that patients with BRCA1/2 mutations dem-
onstrated superior response rates (68 vs. 33.3%) and progression
free survival (6.8 vs. 4.8 months) with carboplatin compared with
docetaxel [29].
4.6. Eribulin
It is a microtubule inhibitor approved for the treatment of meta-
static breast cancer in patients who had received 1 or more chem-
otherapy regimens including an anthracycline and a taxane.
Data from two large multicenter trials (Study 305 and 301) was
collectively analyzed to assess the efficacy of eribulin in various
subgroups of patients with metastatic breast cancer. In study
“305” patients were randomized to Eribulin or treatment of clini-
cians choice after failure of 2 or more chemotherapeutic agents
whereas in study “301” patients were randomized to eribulin or
capecitabine. There were 1644 patients in both studies combined
out of which 352 were triple negative. Median overall survival (15
vs. 12.6 months p<0.01) and progression free survival (3.9 vs. 3.2
months p<0.05) was significantly longer with eribulin compared
to control arm respectively. The overall response rate was same in
both groups whereas clinical benefit rate was again significantly
superior with eribulin (30% vs. 27% p<0.05). The superiority of
overall survival and progression free survival with eribulin was
also seen in patients with triple negative breast cancer (12.4 vs.
8.1 months P<0.01) (2.8 vs. 2.5 months p=0.028) [30].
4.7. Ixabepilone
It is an Epothilone B analogue approved as single agent in patients
with metastatic breast cancer resistant to anthracyclines, taxanes
and capecitabine.
A retrospective analysis of 5 phase II trials was conducted by
Perez et al to see its efficacy in triple negative breast cancer pa-
tients. The overall response rates in these trials with pretreatment
status of no chemotherapy to progression on several lines ranged
from 6 to 55%. Median PFS was 5.7 months whereas median OS
was 8.6 months
[31,32].
5. Combination Chemotherapy
5.1. CMF (Cyclophosphamide, Methotrexate, 5 FU)
It is one of the oldest chemotherapy protocol which lost its popu-
larity after the introduction of anthracyclines and taxanes. Clas-
sical CMF (orally administered cyclophosphamide) was com-
pared with intravenously administered CMF and demonstrated
response rates of 44.5% and 39% respectively. PFS and OS were
similar in both groups but patient’s acceptance was better for in-
travenous CMF [33].
Superior palliation is achieved with high dose CMF at the cost of
increased toxicity. A randomized trial was conducted in which
2 different dosage schemes of CMF in patients with metastatic
breast cancer were evaluated. Doses on the higher-dose arm
were 40 mg/m2 (M) and 600 mg/m2 (C,F); doses on the lower-
dose arm were 20 mg/m2 (M) and 300 mg/m2 (C,F). Response
rates were 30% vs. 11% and median survival was 15.6 months vs.
12.8 months in higher dose vs. lower dose arm [34].
CMF may have a substantial role in triple negative breast cancer.
Munzone et al. [35] in their review explored the potential benefit
of CMF in adjuvant setting. Cells that lack BRCA 1 have shown
an In vitro sensitivity to chemotherapies causing double strand
breaks in DNA such as 5 FU. Furthermore, antimetabolites like
MTX and 5 FU are appropriate for rapid proliferation index as-
sociated with TNBC. The greater sensitivity observed with these
agents’ warrants further clinical studies in evaluation of its role
in metastatic triple negative breast cancer.
5.2. FAC (5 FU, Doxorubicin, Cyclophosphamide)/ FEC (5 FU,
Epirubicin, Cyclophosphamide)
FEC is therapeutically equivalent to FAC but with reduced tox-
icity. M Lopez et al compared FAC and FEC. The objective re-
sponse rates were 46% with FAC and 44% with FEC. There was
no difference in PFS and OS between the two arms. Toxicities
were more frequently seen in patients receiving FAC [36].
5.3. Anthracyclines/Taxanes combinations
A phase III trial was designed to compare AC, single agent doc-
etaxel and AC followed by docetaxel as first line chemotherapy
in metastatic breast cancer. The overall response rates were 30%
for AC, 41% for docetaxel and 35% for AC followed by docetaxel.
The median PFS was 6.4, 6.4 and 6.7 months in AC, Docetaxel
(D) and AC followed by docetaxel arms and median overall sur-
vival was 22.6, 25.7 and 25 months in AC, D and AC-D arms
respectively.
Although there was no difference in PFS in between the three
Volume 1 Issue 4-2018 Review Article
United Prime Publications: http://unitedprimepub.com 4
5. arms, nonetheless, there was a trend favoring docetaxel alone
arm in terms of RR and OS [37]. AT failed to demonstrate supe-
riority over AC. EORTC group compared AC (doxorubicin and
cyclophoshamide) with AT (doxorubicin and paclitaxel) in pa-
tients with metastatic breast cancer. The response rates were 58%
vs. 54% and median overall survival was 20.6 vs. 20.5 months in
AT and AC arms respectively. Median PFS was 6 months in both
groups. AT regimen was more toxic with 32% incidence of febrile
neutropenia in contrast to 9% seen in patients receiving AC [38].
AT is more efficacious when compared with FAC. Bontenbal
et al conducted a phase III study comparing Doxorubicin and
Docetaxel combination (AT) with FAC in metastatic breast can-
cer patients. Median time to progression and median OS were
significantly longer for patients on AT compared with FAC (8.0
vs. 6.6 months P = .004; OS: 22.6 vs. 16.2 months P = .019). The
overall response rates were also significantly higher in patients
on AT regimen i.e 58 vs. 37%. The incidence of neutropenic fever
was higher in patients treated with doxorubicin and Docetaxel
combination (33% vs. 9% p<0.001) [39].
No difference in efficacy was found between EC (Epirubicin
and cyclophosphamide) and ED (Epirubicin and Docetaxel) in
a randomized phase III trial conducted by Blohmer et al. [40].
Similarly, in another study by Langely et al. [41] Epirubicin and
Paclitaxel (EP) failed to prove its superiority over Epirubicin and
Cyclophosphamide (EC) in terms of PFS and OS.
These diverse results attained for Anthracyclines vs. Taxanes
combination in metastatic breast cancer patients necessitates
further clinical studies.
5.4. Capecitabine Combinations
Capecitabine (X) plus Docetaxel (T) is superior to Docetaxel (T)
alone in metastatic breast cancer. A phase III randomized trial
compared XT with T alone in patients with metastatic breast can-
cer previously treated with anthracyclines. The overall response
rates were 42% with XT and 30% with T(p=0.006). The Median
PFS and OS were significantly higher for XT as compared to T
monotherapy (6.1 vs. 4.2 months), (14.5 vs. 11.5 months) (42)
.
This was the first phase III clinical trial in which combination
chemotherapy provided a significant survival advantage over
single agent chemotherapy.
An additional randomized trial was conducted comparing con-
comitant administration of capecitabine and docetaxel with se-
quential single agent docetaxel followed by capecitabine on pro-
gression in patients with metastatic breast cancer. Combination
capecitabine and docetaxel were significantly better over sequen-
tial administration of docetaxel and capecitabine [43].
A phase III study evaluated the role of maintenance capecit-
abine in triple negative breast cancer patients who responded to
capecitabine and docetaxel. The median PFS in the capecitabine
maintenance group and non maintenance group was 10.1 vs. 6.7
months respectively (p=0.003). However, there was no signifi-
cant difference in toxicities between the two groups [44].
Docetaxel Cisplatin may be superior to Docetaxel Capecitabine
in first line treatment of metastatic triple negative breast can-
cer. Patients were randomized to receive either docetaxel cispl-
atin or docetaxel capecitabine. Overall response rates (63% vs.
15.4% p=0.001), PFS (10.9 vs. 4.8 months p<0.001) and OS (32.8
months versus 21.5 months P = 0.027) were significantly higher
in docetaxel cisplatin arm [45].
Ixabepilone and Capecitabine doublet demonstrated superior
outcome in contrast to capecitabine alone in metastatic triple
negative breast cancer patients previously treated with anthracy-
clines and taxanes. A study was designed to evaluate the efficacy
of capecitabine plus Ixabepilone vs. capecitabine alone. The trial
demonstrated superior PFS (5.8 vs. 4.2 months P<0.0003) and
overall response rates (35% vs. 14% P<0.0001) with the doublet
as compared to monotherapy. Nonetheless Grade 3/4 toxicities
were more commonly seen in Ixabepilone and capecitabine arm
[46].
5.5. Platinum Combinations
Platinums are being extensively investigated in patients with tri-
ple negative breast cancer.
A retrospective analysis was conducted to see the response of pa-
clitaxel and carboplatin in metastatic triple negative breast can-
cer patients. The overall response was 57% and median PFS was
16 weeks with this regimen [47].
CBCSG006 was a randomized open label phase III trial compar-
ing cisplatin and gemcitabine with paclitaxel and gemcitabine as
first line for patients with metastatic triple negative breast can-
cer. Median PFS was 7.73 months with cisplatin plus gemcitabine
and 6.47 months with paclitaxel plus gemcitabine [48].
The tnAcity study is phase II/III assessing efficacy and safety of
first line nab paclitaxel plus gemcitabine or carboplatin versus
gemcitabine carboplatin as first line treatment of patients with
metastatic triple negative breast cancer. The results of phase II
portion were presented in San Antonio Breast cancer sympo-
sium in Dec 2016. The
median PFS was significantly higher with nab Paclitaxel carbopl-
atin vs. either nab-Paclitaxel Gemcitabine or Gemcitabine Car-
boplatin (7.4 vs 5.4 months, P = 0.03 and 7.4 vs 6.0 months, P =
0.02) [49].
Fewer studies have been carried out evaluating the role of lipopl-
Volume 1 Issue 4-2018 Review Article
United Prime Publications: http://unitedprimepub.com 5
6. atin doublets in patients with metastatic breast cancer. One such
study was conducted by Farhat et al. [50] in which patients were
enrolled to receive lipoplatin and vinorelbine. The objective re-
sponse rate was 53.1% with complete response seen in 3 patients
(9.4%). Median PFS was 8 months and OS was 21 months.
6. Ongoing Chemotherapy Trials in Metastatic Breast
Cancer
Platinum rechallenge in patients with platinum sensitive mTN-
BC. (ClinicalTrials.gov Identifier: NCT02607215)
A double blind study of Paclitaxel in combination with Reparixin
or Placebo for metastatic triple negative breast cancer. (Clinical-
Trials.gov Identifier: NCT02370238) Ph3 study to determine
safety, tolerability & tumor response of Oraxol compared to
Taxol in metastatic breast cancer. (ClinicalTrials.gov Identifier:
NCT02594371) Capecitabine Maintenance Therapy Following
Capecitabine Combined With Docetaxel in Treatment of mBC.
(ClinicalTrials.gov Identifier: NCT01917279) A Phase Ib/II
Study of Eribulin in Combination With Cyclophosphamide in
Patients With Solid Tumor Malignancies.
(ClinicalTrials.gov Identifier: NCT01554371)
7. At Present Chemotherapy is the Mainstay of Treat-
ment and no Targeted Agents are Approved for the Man-
agement of Patients with Triple Negative Breast Cancer
7.1. Below we will Highlight Investigational Agents Targeting
Subtypes of Triple Negative Breast Cancer
7.2. Androgen Receptor Inhibitors
Androgen receptor inhibitors under active investigation in lu-
minal subtype characterized by androgen signaling TNBC are:
7.3. Enzalutamide
The drug had been evaluated in a phase II study in patients with
advanced androgen receptor positive TNBC. The clinical benefit
rate was 35% at 16 weeks and 29% at 24 weeks. The overall re-
sponse rate observed was 8% and median PFS was 14.7 weeks.
Fatigue, nausea and anorexia were the most common treatment
related adverse events [51].
An ongoing phase III ENDEAR trial will evaluate the role of en-
zalutamide in combination with paclitaxel or as monotherapy vs.
placebo with paclitaxel in patients with advanced stage TNBC.
7.4. Bicalutamide
Another drug evaluated in patients with advanced androgen re-
ceptor positive TNBC. Bicalutamide was given in a dose of 150
mg/day. The clinical benefit rate was 19% and median PFS was
12 weeks [52].
An ongoing trial at MSKCC is evaluating the role of bicalutamide
in combination with CDK4/6 inhibitor Palbociclib in patients
with androgen receptor positive metastatic breast cancer.
7.5. Abiraterone Acetate
An additional phase II trial investigated the role of abiraterone
acetate. Patients were randomized to receive abiraterone and
prednisone, abiraterone, prednisone and exemestane or exemes-
tane alone. Although not statistically significant ORR was supe-
rior in patients receiving abiraterone, prednisone and exemes-
tane [53].
7.6. Other antiandrogenic agents
Another novel agent under exploration in this subtype of triple
negative breast cancer is Orteron et al. [54] a 17,20 lyase inhibitor
which is a key enzyme in androgen synthesis.
8. Tumor Infiltrating Lymphocytes and Immunomodu-
latory Agents
Tumor infiltrating lymphocytes have been suggested as a marker
of immune response. It predicts both prognosis and response to
treatment. Increased levels of either intratumoral or stromal T
cells are associated with improved OS and DFS in TNBC as com-
pared to other subtypes of breast cancer [55]. Growing interest is
seen in targeting immune system in patients with triple negative
breast cancer. New immune modulatory agents including im-
mune check point inhibitors have shown promising activity in
certain subtypes of TNBC.
KEYNOTE 086 trial is a Phase II trial evaluating the role of Pem-
brolizumab (PD-L1 inhibitor) in heavily treated TNBC patients
(Cohort A). The ORR observed was 4.7% and stable disease was
seen in 20.6% patients. The median duration of response was 6.3
months. The response was independent of tumor PD-L1 expres-
sion (ORR 4.8% in PD-L1 positive patients vs. 4.7% in PD-L1
negative patients) and was relatively inferior in patients with
poor prognostic factors (ORR 2% in patients with elevated LDH
vs. 7% in patients with normal LDH). The median PFS was 2
months and OS was 8.9 months. Cohort B of KEYNOTE 086
trial included untreated PD-L1 expressing TNBC. The ORR ob-
served in this cohort was 23% with complete response of 4% [56].
9. PARP Inhibitors
The OlympiAD Trial evaluated the role of PARP inhibitors in
patients with inherited BRCA mutated metastatic breast can-
cer. Median PFS was 7 months with Olaparib and 4 months
with standard therapy (HR for progression or death, 0.58; 95%
CI, 0.43-0.8; P<0.001). The RR was 59.9% in Olaparib arm and
28.8% in standard therapy arm thus revealing the potential of
this new class to deliver better results for patients with BRCA
Volume 1 Issue 4-2018 Review Article
United Prime Publications: http://unitedprimepub.com 6
7. positive breast cancer [57].
10. Conclusion
Metastatic triple negative breast cancer is a heterogeneous group
of diseases with variable response rates.
Anthracyclines and taxanes are still preferred by many oncolo-
gists as first line whereas role of platinums in patients with BRCA
mutation need to be elucidated further. Recent insight into
subtypes of TNBC and selective targeted therapies may help to
improve the prognosis. Participation in clinical trials should be
encouraged so as to gain more understanding into this diverse
group of disease.
References
1. M Ghoncheh, Z Pournamdar, H Salehiniya. Incidence and mortality
and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev.
2016;17:S3 43-6.
2. Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altek-
ruse, et al. (Eds.). SEER cancer statistics review. 2012;1975-2009.
3. Clarke M, Collins R, Darby S, Davies C, Evans V, Godwin J, et al. Ef-
fects of chemotherapy and hormonal therapy for early breast cancer on
recurrence and 15-year survival: An overview of the randomised trials.
Lancet. 2005;365:1687-717.
4. Mahmood H, Faheem M, Mehmood S. Association of menopausal
status with pathological features of tumor in stage I to III A Breast Can-
cer patients treated with upfront modified radical mastectomy. J Cancer
PrevCurr Res. 2016;4(1):00109.
5. Gilani GM, Kamal S, Akhter AS. A Differential Study of Breast Cancer
Patients in Punjab, Pakistan. JPMA.2003;53(10): 478.
6. D’Hondt R, Spoormans I, Neyens N, Mortier N, Van Aelst F. Survival
of patients with metastatic breast cancer-a single center experience. Ac-
taClin Belg. 2014;69(3):194-9.
7. Abramson VG, Mayer IA. Molecular heterogeneity of Triple Negative
Breast Cancer. Curr Breast Cancer Rep. 2014;6(3):154-58.
8. Kassam F, Enright K, Dent R, Dranitsaris G, Myers J, Flynn C, et al.
Survival outcomes for patients with metastatic triple negative breast can-
cer: Implications for clinical practice and trial design. Clin Breast Can-
cer. 2009;9(1):29-33.
9. Lin NU, Claus E, Sohl J, Razzak AR, Arnaout A, Winer EP. Sites of
distant recurrence and clinical outcomes in patients with metastatic
triple-negative breast cancer: High incidence of central nervous system
metastases. Cancer. 2008;113(10):2638-45.
10. Milesa D, Minckwitzb GV, Seidmanc AD. Combination Versus Se-
quential Single-Agent Therapy in Metastatic Breast Cancer. Oncologist.
2002;7:13-19.
11. Dear RF, McGeechan K, Jenkins MC, Barratt A, Tattersall
MH, Wilcken N. Combination versus sequential single agent che-
motherapy for metastatic breast cancer.Cochrane Database Syst Rev.
2013;(12):CD008792.
12. Ahmann DL, Bisel HF, Eagan RT. Controlled evaluation of adriamy-
cin (NSC-123127) in patients with disseminated breast cancer. Cancer
Chemother Rep. 1974;58:877-82.
13. Harris L, Batist G, Belt R, Rovira D, Navari R, Azarnia N, et al. Lipo-
some-encapsulated doxorubicin compared with conventional doxoru-
bicin in a randomized multicenter trial as first-line therapy of metastatic
breast carcinoma. Cancer.2002; 94:25-36.
14. Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom
PK, et al. Randomized phase III trial of weekly compared with every-
3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all
HER-2 overexpressors and random assignment to trastuzumab or not in
HER-2 nonoverexpressors: final results of Cancer and Leukemia Group
B protocol 9840. J ClinOncol. 2008;26(10):1642-9.
15. Vu T, Ellard S, Speers CH, Taylor SCM, de Lemos ML, Hu F, et al.
Survival outcome and cost-effectiveness with docetaxel and paclitaxel in
patients with metastatic breast cancer: a population-based evaluation.
Ann Oncol. 2008; 9 (3): 461-464.
16. Ravdin P, Erban J, Overmoyer B et al. Phase III comparison of
docetaxel and paclitaxel in patients with metastatic breast cancer. Eur J
Cancer 2003;1(suppl 5):S201.
17. Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P,
et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared
with polyethylated castor oil-based paclitaxel in women with breast can-
cer. J ClinOncol. 2005;23(31):7794-803.
18. Arpino G, De Placido S, De Angelis C. Nab-paclitaxel for the man-
agement of triple-negative metastatic breast cancer: a case study. Anti-
cancer Drugs. 2015;26(1):117-22.
19. Braiteh F. Nab-Paclitaxel outduels paclitaxel in HR+/Her2- and tri-
ple negative MBC. Oncolive. Miami Breast Cancer Conference. 2016.
20. Kotsori AA, Dolly S, Sheri A, Parton M, Shaunak N, Ashley S, et
al. Is capecitabine efficacious in triple negative metastatic breast cancer.
Oncology. 2010;79(5-6):331-6.
21. Talbot DC, Moiseyenko V, Van Belle S, O’Reilly SM, Alba Conejo E,
Ackland S, et al. Randomised, phase II trial comparing oral capecitabine
(Xeloda) with paclitaxel in patients with metastatic/advanced breast
cancer pretreated with anthracyclines. Br J Cancer. 2002;86:1367-72.
22. Bajetta E, Procopio G, Celio L, Gattinoni L, Della Torre S, Mari-
ani L, et al. Safety and efficacy of two different doses of capecitabine in
the treatment of advanced breast cancer in older women. J ClinOncol
2005;23:2155-61.
Volume 1 Issue 4-2018 Review Article
United Prime Publications: http://unitedprimepub.com 7
8. 23. Harbeck N, Saupe S, Jäger E, Schmidt M, Kreienberg R, Müller L,
et al. A randomized phase III study evaluating pegylated liposomal
doxorubicin versus capecitabine as first-line therapy for metastatic
breast cancer: results of the PELICAN study. Breast Cancer Res Treat.
2017;161(1):63-72.
24. Rha SY, Moon YH, Jeung HC, Kim YT, Sohn JH, Yang WI, Suh
CO, et al. Gemcitabine monotherapy as salvage chemotherapy in
heavily pretreated metastatic breast cancer. Breast Cancer Res Treat.
2005;90(3):215-21.
25. Feher O, Vodvarka P, Jassem J, Morack G, Advani SH, Khoo KS, et
al. First-line gemcitabine versus epirubicin in postmenopausal women
aged 60 or older with metastatic breast cancer: a multicenter, random-
ized, phase III study. Ann Oncol. 2005;16(6):899-908.
26. Zelek L, Barthier S, Riofrio M, Fizazi K, Rixe O, Delord JP, et al.
Weekly vinorelbine is an effective palliative regimen after failure with
anthracyclines and taxanes in metastatic breast carcinoma. Cancer.
2001;92(9):2267-72.
27. Vogel C, O’Rourke M, Winer E, Hochster H, Chang A, Adamkie-
wicz B, et al. Vinorelbine as first-line chemotherapy for advanced breast
cancer in women 60 years of age or older. Ann Oncol. 1999;10(4):397-
402.
28. Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, et al. TB-
CRC009: A Multicenter Phase II Clinical Trial of Platinum Monother-
apy With Biomarker Assessment in Metastatic Triple-Negative Breast
Cancer. Journal of Clinical Oncology. 2015; 33 (17):1902-9.
29. Tutt A, Ellis P, Kilburn L, Gilett C, Pinder S, Abraham J, et al. The
TNT trial: A randomized phase III trial of carboplatin (C) compared
with docetaxel (D) for patients with metastatic or recurrent locally ad-
vanced triple negative or BRCA1/2 breast cancer (CRUK/07/012) [ab-
stract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San
Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX.
Philadelphia (PA): AACR; Cancer Res. 2015;75(9 Suppl):S3-01.
30. Pivot X, Marmé F, Koenigsberg R, Guo M, Berrak E, Wolfer A.
Pooled analyses of eribulin in metastatic breast cancer patients with at
least one prior chemotherapy. Annals of Oncology. 2016;27:1525-31.
31. Tkaczuk KH. Ixabepilone as Monotherapy or in Combination with
Capecitabine for the Treatment of Advanced Breast Cancer. Breast
Cancer (Auckl). 2011;5:1-14.
32. Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et
al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study
of patients with advanced breast cancer resistant to an anthracycline, a
taxane, and capecitabine. J Clin Oncol. 2007;25(23):3407-14.
33. Brandi M, Demitrio A, Ditonno P, Catino A, Lorusso V, Delena
M. Oral versus intravenous CMF in metastatic breast-cancer - a ran-
domized study. Int J Oncol. 19944(3):559-65.
34. Tannock IF, Boyd NF, DeBoer G, Erlichman C, Fine S, Larocque
G, et al. A randomized trial of two dose levels of cyclophosphamide,
methotrexate, and fluorouracil chemotherapy for patients with meta-
static breast cancer. J Clin Oncol. 1988;6(9):1377-87.
35. Munzone E, Curigliano G, Burstein HJ, Winer EP, Goldhirsch A.
CMF revisited in the 21st century. Ann Oncol. 2012;23:305-11.
36. Lopez M, Papaldo P, Di Lauro L, Vici P, Carpano S, Conti EM.
5-Fluorouracil, adriamycin, cyclophosphamide (FAC) vs. 5-fluoroura-
cil, epirubicin, cyclophosphamide (FEC) in metastatic breast cancer.
Oncology. 1989;46(1):1-5.
37. Katsumata N, Watanabe T, Minami H, Aogi K, Tabei T, Sano M,, et al.
Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel,
and alternating AC and docetaxel as front-line chemotherapy for meta-
static breast cancer: Japan Clinical Oncology Group trial (JCOG9802).
Ann Oncol. 2009;20:1210-5.
38. Biganzoli L, Cufer T, Bruning P, Coleman R, Duchateau L, Calvert
AH, et al. Doxorubicin and Paclitaxel Versus Doxorubicin and Cyclo-
phosphamide as First-Line Chemotherapy in Metastatic Breast Cancer:
The European Organization for Research and Treatment of Cancer
10961 Multicenter Phase III Trial. Clinical Oncology. 2002; 20 (14):
3114-21.
39. Bontenbal M, Creemers GJ, Braun HJ, de Boer AC, Janssen JT, Leys
RB, et al. Phase II to III Study Comparing Doxorubicin and Docetaxel
With Fluorouracil, Doxorubicin, and Cyclophosphamide As First-Line
Chemotherapy in Patients With Metastatic Breast Cancer: Results of
a Dutch Community Setting Trial for the Clinical Trial Group of the
Comprehensive Cancer Centre. J Clin Oncol. 2005;23(28):7081-8.
40. Blohmer JU, Schmid P, Hilfrich J, Friese K, Kleine-Tebbe A, Koelbl H,
et al. Epirubicin and cyclophosphamide versus epirubicin and docetaxel
as first-line therapy for women with metastatic breast cancer: Final re-
sults of a randomised phase III trial. Ann Oncol. 2010;21(7):1430-5.
41. Langley RE, Carmichael J, Jones AL, Cameron DA, Qian W, Uscin-
ska B, et al. Phase III Trial of Epirubicin Plus Paclitaxel Compared With
Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for
Metastatic Breast Cancer: United Kingdom National Cancer Research
Institute Trial AB01. J Clinical Oncology. 2005;23(33):8322-30.
42. O’Shaughnessy J, Miles D, Vukelja S et al. Superior survival with
capecitabine plus docetaxel combination therapy in anthracycline-pre-
treated patients with advanced breast cancer: phase III trial results. J
Clin Oncol. 2002;20:2812-23.
43. Beslija S, Obralic N, Basic H. A single institution randomized trial
of Taxotere (T) and Xeloda (X) given in combination vs. Taxotere (t)
followed by Xeloda (x) after progression as first line chemotherapy (CT)
for metastatic breast cancer (MBC). EJC Suppl. 2005;3:114.
44. Liang X, Di L, Song G, Yan Y, Wang C, Jiang H, et al. Capecitabine
Volume 1 Issue 4-2018 Review Article
United Prime Publications: http://unitedprimepub.com 8
9. maintenance therapy for XT chemotherapy-sensitive patients with
metastatic triple-negative breast cancer. Chin J Cancer Res. 2014;
26(5):550-7.
45. Fan Y, Xu BH, Yuan P, Ma F, Wang JY, Ding XY, et al. Docetaxel–
Cisplatin Might Be Superior to Docetaxel– Capecitabine in the First-
line Treatment of Metastatic Triple-negative Breast Cancer. Ann Oncol.
2013;24(5):1219-25.
46. Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, et al.
Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing
After Anthracycline and Taxane Treatment. Journal of Clinical Oncol-
ogy. 2007;25(33):5210-7.
47. Chia JW, Ang P, See H. Triple Negative Metastatic/Recurrent Breast
Cancer: Treatment with Paclitaxel/Carboplatin Combination Chemo-
therapy. Journal of Clinical Oncology. 2007;25:1086.
48. Hu XC, Zhang J, Xu BH, Cai L, Ragaz J, Wang ZH, et al. Cispla-
tin plus gemcitabine versus paclitaxel plus gemcitabine as first line
therapy for metastatic triple negative breast cancer CBCSG006: a ran-
domized open label multicenter phase III trial. The Lancet Oncology.
2015;16(4):436-46.
49. Yardley DA, Coleman RE, Conte PF, Cortes J, Brufsky A, Shtivel-
band M, et al. Nab-paclitaxel + carboplatin or gemcitabine vs gem-
citabine/carboplatin as first-line treatment for patients with triple-
negative metastatic breast cancer: Results from the randomized phase
2 portion of the tnAcity trial [abstract]. In: Proceedings of the 2016 San
Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX.
Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-
15-03.
50. Farhat F, Temraz S, Kattan J. Preliminary Results of a Phase II
Study of Lipoplatin (Liposomal Cisplatin)/Vinorelbine Combination as
First Line Treatment in HER2/Neu Negative Metastatic Breast Cancer
(MBC). Clinical Breast Cancer. 2011;11(6):384-9.
51. Traina TA, Miller K, Yardley DA. Results from a phase 2 study of
enzalutamide, an androgen receptor inhibitor, in advanced AR+ triple-
negative breast cancer. J Clin Oncol. 2015;33(suppl):1003.
52. Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, et al.
Phase II trial of bicalutamide in patients with androgen receptor posi-
tive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer
Res. 2013;19(19):5505-12.
53. O’Shaughnessy J, Campone M, Brain E. Randomized phase 2 study
of abiraterone acetate with or without exemestane in postmenopausal
patients with estrogen receptor-positive metastatic breast cancer. J Clin
Oncol. 2014;32:5.
54. ClinicalTrials.gov. Orteronel as monotherapy in patients with meta-
static breast cancer (MBC) that expresses the androgen receptor (AR).
2016.
55. Disis ML, Stanton SE. Triple-Negative Breast Cancer: Immune
Modulation as the New Treatment Paradigm. ASCO Educational Book.
2015.
56. Adams S, Schmid P, Rugo HS, et al. Phase 2 study of pembrolizumab
(pembro) monotherapy for previously treated metastatic triple-nega-
tive breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol.
2017;35.
57. Robson M, Im SA, Senkus E. Olaparib for metastatic breast cancer in
patients with a germline BRCA mutation. N Engl J Med. 2017;377:523-
33.
Volume 1 Issue 4-2018 Review Article
United Prime Publications: http://unitedprimepub.com 9