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
1) The PORTEC-1 and PORTEC-2 trials compared pelvic radiotherapy to no additional treatment or vaginal brachytherapy for patients with endometrial carcinoma. PORTEC-1 found pelvic radiotherapy reduced vaginal recurrence while PORTEC-2 found vaginal brachytherapy achieved excellent vaginal control with fewer side effects compared to pelvic radiotherapy.
2) The PORTEC-3 trial randomized 686 patients with high risk endometrial cancer to chemoradiotherapy or radiotherapy alone. It found chemoradiotherapy improved failure-free survival compared to radiotherapy alone, especially for stage III patients, but with increased toxicity.
3)
This document summarizes the results of two randomized controlled trials (PORTEC-1 and PORTEC-2) that compared pelvic external beam radiotherapy (EBRT) to vaginal brachytherapy (VBT) or no additional treatment (NAT) for patients with endometrial carcinoma. PORTEC-1 showed that EBRT improves local control over NAT but does not provide a survival benefit and is associated with long-term side effects. PORTEC-2 found that VBT achieves similar local control as EBRT with fewer side effects, establishing VBT as the preferred adjuvant treatment for high intermediate risk patients.
This document summarizes management strategies for metastatic hormone receptor positive breast cancer. It discusses that hormone receptor positive disease has better survival rates than other subtypes. Roughly 30% of early breast cancer patients will develop advanced or metastatic disease, with 6-10% presenting with metastases initially. Treatment modalities discussed include reducing estrogen production, selective estrogen receptor modulators like tamoxifen, aromatase inhibitors, fulvestrant, progestins, targeted therapies, CDK4/6 inhibitors, PI3K/AKT/mTOR pathway inhibitors, and mTOR inhibitors. Combination treatment strategies are also summarized.
1) Endocrine therapy targets the estrogen receptor and is effective in treating hormone receptor positive breast cancers. Tamoxifen has been the standard adjuvant treatment since the 1970s.
2) Guidelines recommend 5 years of tamoxifen therapy for postmenopausal patients and those with hormone receptor positive cancers. Longer durations do not provide additional benefits and may cause harms.
3) While tamoxifen is not effective for hormone receptor negative cancers, some low response may occur due to indirect effects. 20mg daily is the standard tamoxifen dose.
APBI Accelerated Partial Breast Irradiation in Early Breast CancerAjay Sasidharan
Accelerated Partial Breast Irradiation (APBI) delivers radiation to a smaller volume of breast tissue around the lumpectomy cavity using fewer fractions over a shorter period compared to whole breast irradiation. There is growing evidence that APBI is a feasible option with acceptable toxicity for select early-stage breast cancer patients based on phase II and III trials. However, long-term efficacy data are still limited and the largest randomized trial, NSABP B-39/RTOG 0413, is accruing patients to further evaluate outcomes of APBI compared to whole breast irradiation. This trial will provide important data on local control, survival, quality of life, and identify the most suitable patient population for APBI.
Hormonal therapy plays an important role in the treatment of breast cancer. Estrogen exposure is a major risk factor for breast cancer, so therapies aim to reduce estrogen levels or block its effects. Selective estrogen receptor modulators (SERMs) like tamoxifen act as antagonists in breast tissue. Aromatase inhibitors prevent aromatization of androgens to estrogens in postmenopausal women. LHRH agonists suppress ovarian function. Oophorectomy was one of the earliest hormonal therapies used but had significant morbidity. Modern therapies like tamoxifen, aromatase inhibitors, and LHRH agonists are better tolerated and more effective, improving outcomes for breast cancer patients.
Update on Management of Triple Negative Breast Cancerspa718
This document provides an update on the management of triple negative breast cancer from Dr. Banu Arun at MD Anderson Cancer Center. It discusses that triple negative breast cancer is a heterogeneous disease comprised of several molecular subtypes with different characteristics and potential treatment targets. Clinical trials exploring chemotherapy regimens, platinum agents, PARP inhibitors, anti-angiogenic drugs, and immunotherapies are summarized. Ongoing research aims to better define the subtypes in order to personalize treatment for triple negative breast cancer patients.
1) The PORTEC-1 and PORTEC-2 trials compared pelvic radiotherapy to no additional treatment or vaginal brachytherapy for patients with endometrial carcinoma. PORTEC-1 found pelvic radiotherapy reduced vaginal recurrence while PORTEC-2 found vaginal brachytherapy achieved excellent vaginal control with fewer side effects compared to pelvic radiotherapy.
2) The PORTEC-3 trial randomized 686 patients with high risk endometrial cancer to chemoradiotherapy or radiotherapy alone. It found chemoradiotherapy improved failure-free survival compared to radiotherapy alone, especially for stage III patients, but with increased toxicity.
3)
This document summarizes the results of two randomized controlled trials (PORTEC-1 and PORTEC-2) that compared pelvic external beam radiotherapy (EBRT) to vaginal brachytherapy (VBT) or no additional treatment (NAT) for patients with endometrial carcinoma. PORTEC-1 showed that EBRT improves local control over NAT but does not provide a survival benefit and is associated with long-term side effects. PORTEC-2 found that VBT achieves similar local control as EBRT with fewer side effects, establishing VBT as the preferred adjuvant treatment for high intermediate risk patients.
This document summarizes management strategies for metastatic hormone receptor positive breast cancer. It discusses that hormone receptor positive disease has better survival rates than other subtypes. Roughly 30% of early breast cancer patients will develop advanced or metastatic disease, with 6-10% presenting with metastases initially. Treatment modalities discussed include reducing estrogen production, selective estrogen receptor modulators like tamoxifen, aromatase inhibitors, fulvestrant, progestins, targeted therapies, CDK4/6 inhibitors, PI3K/AKT/mTOR pathway inhibitors, and mTOR inhibitors. Combination treatment strategies are also summarized.
1) Endocrine therapy targets the estrogen receptor and is effective in treating hormone receptor positive breast cancers. Tamoxifen has been the standard adjuvant treatment since the 1970s.
2) Guidelines recommend 5 years of tamoxifen therapy for postmenopausal patients and those with hormone receptor positive cancers. Longer durations do not provide additional benefits and may cause harms.
3) While tamoxifen is not effective for hormone receptor negative cancers, some low response may occur due to indirect effects. 20mg daily is the standard tamoxifen dose.
APBI Accelerated Partial Breast Irradiation in Early Breast CancerAjay Sasidharan
Accelerated Partial Breast Irradiation (APBI) delivers radiation to a smaller volume of breast tissue around the lumpectomy cavity using fewer fractions over a shorter period compared to whole breast irradiation. There is growing evidence that APBI is a feasible option with acceptable toxicity for select early-stage breast cancer patients based on phase II and III trials. However, long-term efficacy data are still limited and the largest randomized trial, NSABP B-39/RTOG 0413, is accruing patients to further evaluate outcomes of APBI compared to whole breast irradiation. This trial will provide important data on local control, survival, quality of life, and identify the most suitable patient population for APBI.
Hormonal therapy plays an important role in the treatment of breast cancer. Estrogen exposure is a major risk factor for breast cancer, so therapies aim to reduce estrogen levels or block its effects. Selective estrogen receptor modulators (SERMs) like tamoxifen act as antagonists in breast tissue. Aromatase inhibitors prevent aromatization of androgens to estrogens in postmenopausal women. LHRH agonists suppress ovarian function. Oophorectomy was one of the earliest hormonal therapies used but had significant morbidity. Modern therapies like tamoxifen, aromatase inhibitors, and LHRH agonists are better tolerated and more effective, improving outcomes for breast cancer patients.
Update on Management of Triple Negative Breast Cancerspa718
This document provides an update on the management of triple negative breast cancer from Dr. Banu Arun at MD Anderson Cancer Center. It discusses that triple negative breast cancer is a heterogeneous disease comprised of several molecular subtypes with different characteristics and potential treatment targets. Clinical trials exploring chemotherapy regimens, platinum agents, PARP inhibitors, anti-angiogenic drugs, and immunotherapies are summarized. Ongoing research aims to better define the subtypes in order to personalize treatment for triple negative breast cancer patients.
Management Of Recurrent Ovarian Ca (ROC)
The document discusses the management of recurrent ovarian cancer. It provides details on the incidence and patterns of recurrence for ovarian cancer. For patients with platinum-sensitive recurrent ovarian cancer, the standard treatment is second line chemotherapy. Several chemotherapy regimens are discussed including carboplatin with paclitaxel, gemcitabine, or pegylated liposomal doxorubicin. For partially platinum-sensitive recurrent ovarian cancer, the OVA-301 trial showed improved overall survival with the combination of carboplatin and pegylated liposomal doxorubicin compared to carboplatin alone. Management of recurrent ovarian cancer aims to prolong survival, delay progression,
Metastatic breast cancer is incurable but treatable. Treatment goals are to prolong life, control tumor growth, reduce symptoms, and maintain quality of life. Treatment depends on tumor biology including hormone receptor and HER2 status. For hormone receptor positive cancer, endocrine therapy is the primary treatment. Chemotherapy is used for hormone receptor negative cancers or when endocrine therapy fails. New targeted therapies in combination with endocrine therapy or chemotherapy have improved outcomes. Outcomes are better in patients with slower growing tumors, fewer metastases, and less prior treatment. Managing metastatic breast cancer requires serial evaluation and adjustment of treatment over time based on response and symptoms.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
The OUTBACK trial compared standard chemoradiation (CRT) to CRT plus adjuvant carboplatin and paclitaxel (ACT) in patients with locally advanced cervical cancer. Over 900 patients were randomized 1:1 to receive either CRT alone or CRT followed by ACT. Baseline characteristics were well balanced between the two arms. The primary endpoint was overall survival and secondary endpoints included progression-free survival, adverse events, sites of recurrence, and patient-reported outcomes.
The SOFT trial investigated the role of ovarian function suppression (OFS) and aromatase inhibitors (AIs) in premenopausal breast cancer patients. It found that adding OFS to tamoxifen (TAM) improved 5-year disease-free survival from 84.7% to 86.6%, though the difference was not statistically significant. The SOFT+TEXT analysis found that substituting exemestane for TAM when combined with OFS improved 5-year disease-free survival from 87.3% to 91.1%, with a statistically significant difference. For patients who received chemotherapy, exemestane+OFS provided an absolute 5-year breast cancer-free rate improvement of 3.
This downloadable slidedeck, presented in a regional grand rounds series, focuses on increasing awareness about current and emerging treatment options for patients with newly diagnosed and recurrent ovarian cancer.
Join Dr. Erica Mayer, medical oncologist at Dana-Farber/Brigham and Women's Cancer Center, to learn about exciting metastatic breast cancer developments from the past year. Dr. Mayer presents an overview on metastatic breast cancer and the subgroups, including Hormone Receptive, HER2+, and Triple Negative, and highlights recent advances for each of these subgroups. She also discusses the importance of clinical trials and what it means to participate in a clinical trial.
For more information on the Breast Cancer Treatment Center at Dana-Farber Cancer Institute, please visit:
http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-Centers-and-Clinical-Services/Breast-Cancer-Treatment-Center.aspx
This document discusses the management of carcinoma of the esophagus. It begins by outlining treatment approaches for localized versus metastatic disease, including definitive and palliative therapies. It then reviews the evolution of esophageal cancer treatment, including non-surgical approaches using radiation therapy alone or combined modality therapy, as well as surgical treatments. Several studies evaluating different treatment regimens are summarized, including the benefits of concurrent chemoradiation therapy over radiation alone. The role of preoperative chemoradiation is discussed. Techniques for radiation therapy delivery are also outlined. The document concludes by discussing palliative care approaches for esophageal cancer patients.
This document summarizes the results of the PORTEC-3 trial which compared adjuvant chemoradiation therapy (CTRT) to radiation alone in patients with high risk endometrial cancer. The trial included patients with high risk factors like grade 3 endometrioid cancer, stage II-III disease, or clear cell or serous histology. It found that while CTRT improved failure-free survival by 11% compared to radiation alone, there was only a 5% improvement in overall survival. CTRT was also associated with more toxicities but they were generally rapid to recover from. The benefits of CTRT need to be weighed against the increased costs and treatment duration associated with its toxicities. The conclusion
Landmark chemotherapy trials in advanced ovarian cancer established platinum-based combinations as the standard of care. GOG 47 (1986) showed cisplatin improves response rates and progression-free survival compared to cyclophosphamide alone. GOG 111 (1996) found the combination of paclitaxel and cisplatin improved progression-free and overall survival over cyclophosphamide and cisplatin. Subsequent trials determined carboplatin as an effective alternative to cisplatin, with fewer side effects.
1) Hormonal therapy targets estrogen receptor positive breast cancers, which comprise around 70% of cases. It works by blocking the effects of estrogen through various mechanisms.
2) Available hormonal therapies include selective estrogen receptor modulators (SERMs) like tamoxifen, aromatase inhibitors, LHRH analogues, and ovarian ablation through surgery or radiation.
3) In the adjuvant setting, 5 years of tamoxifen reduces recurrence and mortality rates in both pre- and postmenopausal women. Longer durations up to 10 years provide further benefits in high risk patients. Aromatase inhibitors are now preferred over tamoxifen for initial therapy in postmenopausal women.
Role and Side effects of Ovarian Function Suppression in Breast CancerAjeet Gandhi
1) The document discusses the role and side effects of ovarian suppression therapy in premenopausal women receiving adjuvant treatment for hormone receptor positive breast cancer.
2) Key trials like SOFT and TEXT showed that the addition of ovarian suppression to tamoxifen or aromatase inhibitors improved disease-free survival rates and reduced the risk of breast cancer recurrence in premenopausal women compared to tamoxifen alone.
3) The benefits of ovarian suppression were greater in women who remained premenopausal after chemotherapy and those with larger/node-positive tumors or higher grade disease. Common side effects included hot flashes and musculoskeletal symptoms.
Advances In Adjuvant Systemic Therapy Of Breast Cancerfondas vakalis
This document discusses adjuvant systemic therapy options for breast cancer. It provides an overview of chemotherapy, endocrine therapy, targeted therapy and radiotherapy approaches. It also discusses ongoing clinical trials evaluating newer adjuvant treatments and biomarkers to help determine optimal treatment approaches for individual patients.
This document discusses various aspects of managing early stage breast cancer, including:
1. It provides an overview of the evolution of surgical approaches from radical to breast conserving surgery and discusses key trials demonstrating equivalent survival with breast conservation plus radiation compared to mastectomy.
2. It discusses the changing approach to axillary staging from axillary dissection to sentinel lymph node biopsy and trials validating the adequacy of sentinel node biopsy alone in certain cases.
3. It addresses locoregional treatment approaches including the appropriate use of radiation after lumpectomy, mastectomy, and with varying nodal involvement based on guidelines.
Total neoadjuvant therapy for rectal cancer 2016Mohamed Abdulla
1) Total neoadjuvant therapy, consisting of chemotherapy followed by chemoradiation and surgery, may improve outcomes for rectal cancer over the traditional approach.
2) Ongoing clinical trials are investigating selective use of radiation and whether radiation can be omitted from some neoadjuvant regimens based on risk factors and response.
3) Near total neoadjuvant therapy with upfront chemotherapy alone may achieve pathologic complete responses in a third of patients and warrants further exploration as an alternative to traditional chemoradiation.
Axillary radiotherapy provides comparable regional control to axillary lymph node dissection for breast cancer patients with positive sentinel nodes, with fewer side effects. The AMAROS trial found similar 5-year axillary recurrence, disease-free survival, and overall survival between the radiotherapy and dissection groups. However, radiotherapy resulted in significantly less lymphedema. While control was excellent with both treatments, the trial was underpowered to definitively show non-inferiority due to lower-than-expected axillary recurrences.
This document summarizes hormonal treatment for breast cancer, including the history and mechanisms of various endocrine therapies. It discusses the timeline of developments in hormonal therapies from the late 19th century to present, covering areas like surgical oophorectomy, tamoxifen, aromatase inhibitors, and more. Key findings and mechanisms of different therapies like tamoxifen, aromatase inhibitors, and fulvestrant are summarized. The optimal use and duration of adjuvant tamoxifen therapy is discussed based on various clinical trials. The relationship between tamoxifen benefit and estrogen/progesterone receptor status is also covered.
This document summarizes recent advances in endocrine therapy for breast cancer. Key findings from clinical trials show that aromatase inhibitors are superior to tamoxifen for postmenopausal women, 10 years of tamoxifen is better than 5 years for premenopausal women, and combining mTOR inhibitors like everolimus with hormonal therapies improves outcomes. New trials also found fulvestrant works as well as aromatase inhibitors for first-line metastatic disease. Combining fulvestrant and exemestane was more effective than single agents. Exemestane was also found to reduce invasive breast cancers in prevention settings.
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.
Management Of Recurrent Ovarian Ca (ROC)
The document discusses the management of recurrent ovarian cancer. It provides details on the incidence and patterns of recurrence for ovarian cancer. For patients with platinum-sensitive recurrent ovarian cancer, the standard treatment is second line chemotherapy. Several chemotherapy regimens are discussed including carboplatin with paclitaxel, gemcitabine, or pegylated liposomal doxorubicin. For partially platinum-sensitive recurrent ovarian cancer, the OVA-301 trial showed improved overall survival with the combination of carboplatin and pegylated liposomal doxorubicin compared to carboplatin alone. Management of recurrent ovarian cancer aims to prolong survival, delay progression,
Metastatic breast cancer is incurable but treatable. Treatment goals are to prolong life, control tumor growth, reduce symptoms, and maintain quality of life. Treatment depends on tumor biology including hormone receptor and HER2 status. For hormone receptor positive cancer, endocrine therapy is the primary treatment. Chemotherapy is used for hormone receptor negative cancers or when endocrine therapy fails. New targeted therapies in combination with endocrine therapy or chemotherapy have improved outcomes. Outcomes are better in patients with slower growing tumors, fewer metastases, and less prior treatment. Managing metastatic breast cancer requires serial evaluation and adjustment of treatment over time based on response and symptoms.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
The OUTBACK trial compared standard chemoradiation (CRT) to CRT plus adjuvant carboplatin and paclitaxel (ACT) in patients with locally advanced cervical cancer. Over 900 patients were randomized 1:1 to receive either CRT alone or CRT followed by ACT. Baseline characteristics were well balanced between the two arms. The primary endpoint was overall survival and secondary endpoints included progression-free survival, adverse events, sites of recurrence, and patient-reported outcomes.
The SOFT trial investigated the role of ovarian function suppression (OFS) and aromatase inhibitors (AIs) in premenopausal breast cancer patients. It found that adding OFS to tamoxifen (TAM) improved 5-year disease-free survival from 84.7% to 86.6%, though the difference was not statistically significant. The SOFT+TEXT analysis found that substituting exemestane for TAM when combined with OFS improved 5-year disease-free survival from 87.3% to 91.1%, with a statistically significant difference. For patients who received chemotherapy, exemestane+OFS provided an absolute 5-year breast cancer-free rate improvement of 3.
This downloadable slidedeck, presented in a regional grand rounds series, focuses on increasing awareness about current and emerging treatment options for patients with newly diagnosed and recurrent ovarian cancer.
Join Dr. Erica Mayer, medical oncologist at Dana-Farber/Brigham and Women's Cancer Center, to learn about exciting metastatic breast cancer developments from the past year. Dr. Mayer presents an overview on metastatic breast cancer and the subgroups, including Hormone Receptive, HER2+, and Triple Negative, and highlights recent advances for each of these subgroups. She also discusses the importance of clinical trials and what it means to participate in a clinical trial.
For more information on the Breast Cancer Treatment Center at Dana-Farber Cancer Institute, please visit:
http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-Centers-and-Clinical-Services/Breast-Cancer-Treatment-Center.aspx
This document discusses the management of carcinoma of the esophagus. It begins by outlining treatment approaches for localized versus metastatic disease, including definitive and palliative therapies. It then reviews the evolution of esophageal cancer treatment, including non-surgical approaches using radiation therapy alone or combined modality therapy, as well as surgical treatments. Several studies evaluating different treatment regimens are summarized, including the benefits of concurrent chemoradiation therapy over radiation alone. The role of preoperative chemoradiation is discussed. Techniques for radiation therapy delivery are also outlined. The document concludes by discussing palliative care approaches for esophageal cancer patients.
This document summarizes the results of the PORTEC-3 trial which compared adjuvant chemoradiation therapy (CTRT) to radiation alone in patients with high risk endometrial cancer. The trial included patients with high risk factors like grade 3 endometrioid cancer, stage II-III disease, or clear cell or serous histology. It found that while CTRT improved failure-free survival by 11% compared to radiation alone, there was only a 5% improvement in overall survival. CTRT was also associated with more toxicities but they were generally rapid to recover from. The benefits of CTRT need to be weighed against the increased costs and treatment duration associated with its toxicities. The conclusion
Landmark chemotherapy trials in advanced ovarian cancer established platinum-based combinations as the standard of care. GOG 47 (1986) showed cisplatin improves response rates and progression-free survival compared to cyclophosphamide alone. GOG 111 (1996) found the combination of paclitaxel and cisplatin improved progression-free and overall survival over cyclophosphamide and cisplatin. Subsequent trials determined carboplatin as an effective alternative to cisplatin, with fewer side effects.
1) Hormonal therapy targets estrogen receptor positive breast cancers, which comprise around 70% of cases. It works by blocking the effects of estrogen through various mechanisms.
2) Available hormonal therapies include selective estrogen receptor modulators (SERMs) like tamoxifen, aromatase inhibitors, LHRH analogues, and ovarian ablation through surgery or radiation.
3) In the adjuvant setting, 5 years of tamoxifen reduces recurrence and mortality rates in both pre- and postmenopausal women. Longer durations up to 10 years provide further benefits in high risk patients. Aromatase inhibitors are now preferred over tamoxifen for initial therapy in postmenopausal women.
Role and Side effects of Ovarian Function Suppression in Breast CancerAjeet Gandhi
1) The document discusses the role and side effects of ovarian suppression therapy in premenopausal women receiving adjuvant treatment for hormone receptor positive breast cancer.
2) Key trials like SOFT and TEXT showed that the addition of ovarian suppression to tamoxifen or aromatase inhibitors improved disease-free survival rates and reduced the risk of breast cancer recurrence in premenopausal women compared to tamoxifen alone.
3) The benefits of ovarian suppression were greater in women who remained premenopausal after chemotherapy and those with larger/node-positive tumors or higher grade disease. Common side effects included hot flashes and musculoskeletal symptoms.
Advances In Adjuvant Systemic Therapy Of Breast Cancerfondas vakalis
This document discusses adjuvant systemic therapy options for breast cancer. It provides an overview of chemotherapy, endocrine therapy, targeted therapy and radiotherapy approaches. It also discusses ongoing clinical trials evaluating newer adjuvant treatments and biomarkers to help determine optimal treatment approaches for individual patients.
This document discusses various aspects of managing early stage breast cancer, including:
1. It provides an overview of the evolution of surgical approaches from radical to breast conserving surgery and discusses key trials demonstrating equivalent survival with breast conservation plus radiation compared to mastectomy.
2. It discusses the changing approach to axillary staging from axillary dissection to sentinel lymph node biopsy and trials validating the adequacy of sentinel node biopsy alone in certain cases.
3. It addresses locoregional treatment approaches including the appropriate use of radiation after lumpectomy, mastectomy, and with varying nodal involvement based on guidelines.
Total neoadjuvant therapy for rectal cancer 2016Mohamed Abdulla
1) Total neoadjuvant therapy, consisting of chemotherapy followed by chemoradiation and surgery, may improve outcomes for rectal cancer over the traditional approach.
2) Ongoing clinical trials are investigating selective use of radiation and whether radiation can be omitted from some neoadjuvant regimens based on risk factors and response.
3) Near total neoadjuvant therapy with upfront chemotherapy alone may achieve pathologic complete responses in a third of patients and warrants further exploration as an alternative to traditional chemoradiation.
Axillary radiotherapy provides comparable regional control to axillary lymph node dissection for breast cancer patients with positive sentinel nodes, with fewer side effects. The AMAROS trial found similar 5-year axillary recurrence, disease-free survival, and overall survival between the radiotherapy and dissection groups. However, radiotherapy resulted in significantly less lymphedema. While control was excellent with both treatments, the trial was underpowered to definitively show non-inferiority due to lower-than-expected axillary recurrences.
This document summarizes hormonal treatment for breast cancer, including the history and mechanisms of various endocrine therapies. It discusses the timeline of developments in hormonal therapies from the late 19th century to present, covering areas like surgical oophorectomy, tamoxifen, aromatase inhibitors, and more. Key findings and mechanisms of different therapies like tamoxifen, aromatase inhibitors, and fulvestrant are summarized. The optimal use and duration of adjuvant tamoxifen therapy is discussed based on various clinical trials. The relationship between tamoxifen benefit and estrogen/progesterone receptor status is also covered.
This document summarizes recent advances in endocrine therapy for breast cancer. Key findings from clinical trials show that aromatase inhibitors are superior to tamoxifen for postmenopausal women, 10 years of tamoxifen is better than 5 years for premenopausal women, and combining mTOR inhibitors like everolimus with hormonal therapies improves outcomes. New trials also found fulvestrant works as well as aromatase inhibitors for first-line metastatic disease. Combining fulvestrant and exemestane was more effective than single agents. Exemestane was also found to reduce invasive breast cancers in prevention settings.
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.
Hormone therapy is an important treatment for hormone receptor positive breast cancers. Tamoxifen for 5 years and aromatase inhibitors are effective adjuvant therapies. Trials have shown that aromatase inhibitors are superior to tamoxifen alone for postmenopausal women. Sequential therapy with tamoxifen followed by an aromatase inhibitor also improves outcomes compared to tamoxifen alone. Ongoing research continues to refine the optimal duration and sequencing of hormone therapies.
This document discusses endocrine therapy for metastatic breast cancer. It covers several topics:
1) Hormonal therapy is preferred over chemotherapy for bone or soft tissue metastases, while chemotherapy is preferred for high tumor burden or visceral metastases.
2) Oligometastatic disease can be treated with local therapies to achieve complete remission for limited metastatic lesions.
3) Hormonal therapies like tamoxifen and aromatase inhibitors are effective first-line treatments. Ovarian suppression plus tamoxifen improves outcomes over suppression alone.
4) Everolimus plus exocrine therapy improves outcomes for advanced ER+ breast cancer resistant to aromatase inhibitors.
Hormone Thearpy Early Breast Cancer Farshad Modified 2003farshad nejad
The document discusses hormone therapy for early breast cancer. It finds that postmenopausal patients should be treated with an aromatase inhibitor as part of adjuvant therapy. Adjuvant hormone therapy for postmenopausal women with estrogen receptor-positive breast cancer should include an aromatase inhibitor. For premenopausal patients, tamoxifen is the standard treatment, though ovarian suppression may replace chemotherapy in some cases.
Tamoxifen is a selective estrogen receptor modulator used to treat hormone receptor-positive breast cancer. It works by blocking the effects of estrogen in the breast tissue. It is metabolized in the liver into active metabolites that bind to estrogen receptors in tumor cells, inhibiting DNA synthesis and estrogen effects. Common side effects include hot flashes and increased risk of blood clots. Its effectiveness can be reduced by certain antidepressants that inhibit the enzyme needed to metabolize tamoxifen. Genetic testing can help determine if a patient's metabolism makes them less likely to benefit from tamoxifen. Aromatase inhibitors are an alternative class of drugs for breast cancer that work by preventing the conversion of androgens to estrogen in peripheral tissues.
This presentation covers all the basic aspects regarding the breast cancer including the introduction, types, causes, diagnosis and treatment of breast cancer
Breast cancer is the most commonly diagnosed cancer and leading cause of cancer death in women worldwide. Approximately 30% of patients are premenopausal and 10% are aged 35-45 years old. Around 75% of cases are hormone receptor-positive. Treatment options include surgery, chemotherapy, radiotherapy, endocrine therapy, and monoclonal antibody therapy. Estrogens and progesterone are implicated in breast carcinogenesis, so endocrine therapies that block these hormones' effects can treat hormone receptor-positive breast cancer. Tamoxifen, aromatase inhibitors, ovarian suppression, and selective progesterone modulators are some endocrine agents used. Menopause diagnosis is important for determining appropriate endocrine therapy.
1) Adjuvant chemotherapy is recommended for stage III colon cancer and high-risk stage II cancer to reduce the risk of recurrence. 2) For stage III, 5-FU plus folinic acid or capecitabine are standard options, while adding oxaliplatin to these regimens may provide additional benefit. 3) The value of adjuvant therapies like bevacizumab, cetuximab, and irinotecan is still unclear, with studies showing mixed results.
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.
Breast Cancer is the commonest cancer and leading cause of cancer 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 metastatic 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 metastatic disease [4]. A study conducted by Gilani et al. [5] showed
that 25-36% of Pakistani women present with disseminated disease.
Fertility, Pregnancy, Contraception, Lactation And Endocrine Therapy In Breas...Mamdouh Sabry
Discussing every detail concerning gynaecologist and obstetrician in breast cancer. As fertility, pregnancy outcome, contraception, lactation, adjuvant hormone therapy and prevention.
This document summarizes the role of cetuximab in treating squamous cell carcinoma of the head and neck (HNSCC). It discusses clinical trials that showed cetuximab improved survival when combined with radiation for locally advanced HNSCC and improved response rates compared to chemotherapy for recurrent/metastatic HNSCC. The document also reviews the mechanisms of action of cetuximab, potential biomarkers of response, common toxicities, and need for further research to better integrate cetuximab and identify patients most likely to benefit.
This meta-analysis examined four randomized controlled trials comparing aromatase inhibitors to tamoxifen for premenopausal women with hormone receptor-positive breast cancer receiving ovarian suppression. It found that aromatase inhibitors reduced the absolute risk of breast cancer recurrence by 3% compared to tamoxifen at both 5 and 10 years. Subgroup analyses found greater benefit from aromatase inhibitors for HER2-negative disease. Unexpectedly, aromatase inhibitors did not show superiority over tamoxifen for women with four or more involved lymph nodes. The meta-analysis concluded that aromatase inhibitors provided improved disease outcomes over tamoxifen when used with ovarian suppression in premenopausal women.
This document summarizes chemotherapy options for head and neck squamous cell carcinoma (HNSCC). It discusses commonly used chemotherapies like methotrexate, 5-fluorouracil, cisplatin, carboplatin and taxanes. It also covers multi-agent chemotherapy regimens and the roles of neoadjuvant, concurrent and adjuvant chemotherapy when combined with radiation or surgery. Recent advances with targeted therapies like trastuzumab are also mentioned.
L'efficacia clinica del trattamento con ixabepilone nel carcinoma mammario me...Merqurio
1) Approximately 30% of women diagnosed with early-stage breast cancer will progress to metastatic breast cancer, for which treatment options are limited after anthracycline and taxane chemotherapy.
2) Resistance to chemotherapy is a major challenge, as responses to subsequent treatments are typically low (20-30%) and last less than 6 months.
3) Ixabepilone is a potential treatment for taxane-resistant metastatic breast cancer due to its activity against microtubules and lack of cross-resistance with other chemotherapies. It may provide an option for patients with limited remaining treatment options.
This document discusses the management and follow up of gestational trophoblastic neoplasia (GTN). It describes the FIGO prognostic scoring system used to determine risk of chemotherapy resistance. For low risk GTN, single agent chemotherapy with methotrexate or actinomycin is effective. For high risk GTN, multi-agent chemotherapy such as EMA-CO is recommended. Surgical procedures like uterine curettage and hysterectomy may be used in some cases. Strict follow up of beta HCG levels is important after treatment.
This document summarizes the current state of neoadjuvant treatment options for esophageal and gastric cancer. It finds that neoadjuvant therapy prior to surgery should be considered for all patients with greater than T1 or node-positive disease. For esophageal cancer, most patients should receive neoadjuvant chemoradiation. For gastric cancer, there is strong support for adjuvant chemotherapy following surgery. Future areas of research include immunotherapy, targeted therapies, and combination approaches.
Hormone therapy is recommended for women with hormone receptor-positive, non-metastatic breast cancer. Ideal candidates include those who are post-menopausal or have undergone bilateral oophorectomy. Treatment options include tamoxifen, aromatase inhibitors like letrozole or anastrozole, and ovarian suppression with gonadotropin-releasing hormone agonists. While aromatase inhibitors are preferred for post-menopausal women, pre-menopausal high-risk women should receive ovarian suppression plus an aromatase inhibitor. Hormone therapy should be administered for 5 years or longer to reduce the risk of breast cancer recurrence and mortality.
Similar to Systemic therapy stage 4 breast sadia (20)
a brief overview about management of ca breast.pptxSadia Sadiq
This document discusses the management of breast cancer from an oncologist's perspective. It covers topics such as staging, histopathology, treatment including chemotherapy, hormonal therapy, targeted therapy and radiation therapy. Key points discussed include the benefits of neoadjuvant chemotherapy, when radiation therapy is necessary, and clinical trials showing radiation therapy can sometimes be omitted in early breast cancer patients receiving hormonal treatment.
Recurrent Ca Endometrium Vaginal Interstitial.pptxSadia Sadiq
a case of recurrent endometrial cancer with vaginal involvement where free hand needle placement resulted in adequate target coverage and excellent response.
SFRT, also known as GRID therapy, treats tumors with a non-uniform radiation dose to effectively treat the tumor while staying within normal tissue tolerance. It has shown dramatic relief of symptoms, significant tumor regression, and minimal toxicity. Originally introduced in 1909 using perforated screens, modern techniques use MLCs or helical tomotherapy to create GRID-like dosimetry with improved flexibility and dosimetry. Studies show SFRT can achieve high response rates for various tumor types and has potential as a definitive treatment when combined with other therapies. Further clinical trials are warranted to evaluate its safety and efficacy for different cancer indications.
The document discusses the management of the axilla in breast cancer from a radiation oncologist's perspective. It covers how to stage the axilla through physical exam, imaging, or biopsy. For clinically node-negative patients, sentinel lymph node biopsy is standard, while clinically positive nodes may require lymph node dissection. Ongoing trials are exploring omitting further axillary treatment for some patients with positive nodes after neoadjuvant therapy. The conclusion emphasizes that axilla management remains controversial but aims for individualized treatment based on tumor characteristics and response to therapy.
This document discusses total neoadjuvant therapy (TNT) for rectal cancer. It summarizes evidence from trials showing that TNT with chemotherapy prior to chemoradiation and surgery improves pathologic complete response rates and reduces distant metastases compared to adjuvant chemotherapy. The document also reviews the experience with TNT at the author's institution, including a clinical complete response rate of 36% and a pathologic complete response rate of 15.6% among surgery patients. Non-operative management strategies with a watch-and-wait approach are also discussed.
Recent advances in the management of ovarian cancer include:
1) Optimal treatment of early-stage disease involves debulking surgery followed by carboplatin and paclitaxel chemotherapy based on trials showing improved recurrence-free and overall survival.
2) Maintenance therapy with bevacizumab or PARP inhibitors prolongs progression-free survival and overall survival compared to placebo in recurrent platinum-sensitive disease.
3) The role of secondary cytoreductive surgery and intraperitoneal chemotherapy in recurrent disease continues to be evaluated in ongoing clinical trials.
This document discusses the case of a 55-year-old woman diagnosed with Stage IA high-grade serous epithelial ovarian cancer. She underwent surgery followed by 6 cycles of carboplatin/paclitaxel adjuvant chemotherapy. She experienced recurrence 14 months later and underwent a second surgery and 6 cycles of gemcitabine/carboplatin chemotherapy. She had a second recurrence 4 months later and was started on topotecan and bevacizumab, showing a partial response. The document reviews trials on adjuvant chemotherapy for early-stage ovarian cancer and subsequent treatment options for platinum-resistant recurrence.
Advanced breast cancer & chemo by meSadia Sadiq
This document summarizes the presentation of Dr. Sadia Sadiq on locally advanced breast cancer and chemotherapy. The presentation covers staging of breast cancer, local surgical treatments, management of the axilla, adjuvant and neoadjuvant chemotherapy. It discusses the evolution of surgical treatments from radical mastectomy to breast-conserving surgery plus radiation. It also summarizes landmark trials comparing different chemotherapy regimens and the addition of taxanes to anthracycline-based regimens. Finally, it notes that sequential therapy with anthracyclines/alkylators followed by taxanes was proven superior to concurrent taxane-anthracycline-alkylator treatments.
This document provides an overview of multiple myeloma, including its definition, clinical presentation, workup, staging, management, and treatment regimens. Key points include:
- Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in the bone marrow, leading to bone destruction.
- Workup involves blood and urine tests, bone marrow biopsy, skeletal survey, and imaging to determine disease severity and stage according to the Durie-Salmon or ISS staging systems.
- Treatment may include chemotherapy, steroids, immunomodulators, stem cell transplantation, and supportive care. The goal of initial therapy is to achieve remission prior to stem cell transplantation in eligible patients.
Stereotactic body radiation therapy (SBRT) is an evolution of stereotactic radiosurgery that delivers high-dose radiation to tumors in fewer fractions than conventional radiotherapy. It requires extra-ordinary care due to the precision needed to target tumors while sparing surrounding tissues from damage. SBRT has shown efficacy in treating various tumor types including lung, liver, spine, pancreas and prostate cancers with acceptable toxicity risks when proper quality assurance procedures and motion management techniques are followed.
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
- 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
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Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
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 Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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).
2. Breast cancer is the most common malignancy
among females all over the world
3. 5 YEAR SURVIVAL RATES
The overall 5-year survival for all stages combined is 89%
[http://seer.cancer.gov/statfacts/html/breast.html].
However, survival rates vary by stage. 5 year survivals:
[http://seer.cancer.gov/statfacts/html/breast.html].
LOCALIZED DISEASE 99%
REGIONAL DISEASE 85%
METASTATIC DISEASE 26%
4. Clinical Challenges
in the Management of MBC
Individualizing treatment to specific cancer biology
Reducing and managing toxicity of chemotherapies
Understanding and then overcoming resistance to
chemotherapy and hormone therapy
Impact in metastatic and adjuvant settings
Increasing disease control and survival
5. METASTATIC DISEASE
Patients with metastatic cancer can be divided into two
groups:
1. those with stage IV disease at presentation and
2. those who develop metastases after primary treatment.
Biopsy is highly recommended for pathologic
confirmation of presumed metastatic breast cancer and
for marker investigations.
6. The management of stage IV disease depends on the
site and extent of metastases, comorbid conditions, and
clinical tumor characteristics.
Patients with delayed metastatic disease can be divided
into two groups, that is, so-called low-risk
and/or high-risk patients,
7. The low-risk group includes patients
1. who develop metastatic disease after a long
disease-free interval
2. those whose tumors are positive for hormone
receptors
3. those with bone-only disease, and
4. those without extensive visceral organ
involvement.
8. Intermediate-risk or high-risk patients include
those
1. with rapidly progressive disease or
2. visceral involvement and
3. those with disease shown to be refractory to
hormonal manipulation by a prior therapeutic
trial.
9. Low-risk patients who have hormone receptor–positive tumors
should be treated with a trial of hormone therapy.
First-line hormonal therapy consists of an aromatase inhibitor or
tamoxifen, with careful serial assessment of clinical and disease
responses.
10. • Second-line hormonal
agents
The choice of second-line endocrine therapy depends on
the
front-line endocrine agent used. Typically, if tamoxifen was used, the second-
line agent includes an aromatase inhibitor or fulvestrant (Faslodex) for
postmenopausal women.
For premenopausal women, the choice may be megestrol (Megace) or induction
of menopause with an LHRH (luteinizing hormone–releasing hormone) agonist
with or without an aromatase inhibitor.
If aromatase inhibitors were used as front-line agents for postmenopausal
women, second-line options can be to change treatment to include another
class of aromatase inhibitor, or fulvestrant, or tamoxifen.
14. HORMONAL THERAPY IN
METASTATIC SETTING
Pre menopausal :
Tamoxifen is the drug of choice
Response rates range from 16% to 56% (Median 30%) – same as
ovarian ablative techniques.
Overall mean Time to progression for patients with metastatic
disease treated with Tamoxifen is about 6 months
Duration of response is between 12 and 18 months
Tamoxifen plus castration has been shown to have better results
in a meta analysis
15. Ref : Facts and Controversies in Systemic Treatment of Metastatic Breast
Cancer ; CHANTAL BERNARD-MARTY, FATIMA CARDOSO, MARTINE J.
PICCART ; The Oncologist 2004;9:617-632
16. Ref : New directions in hormone therapy for metastatic breast cancer ; M. Namer ;
European Society for Medical Oncology
TAMOXIFEN + OVARIAN SUPRESSION
17. HORMONAL THERAPY IN
METASTATIC SETTING
Post Menopausal
4 major phase III trials have directly compared
Tamoxifen against Aromatase Inhibitors (AI)
All have shown an improvement in time to
progression
The impact on Overall survival not clear however.
In the trial comparing Letrozole to Tamoxifen it was
shown that OS improved in the first 2 yrs.
However no benefit exists at 5yrs.
18. Ref : New directions in hormone therapy for metastatic breast cancer ; M. Namer ;
European Society for Medical Oncology
19. HORMONAL THERAPY IN
METASTATIC SETTING
In case of progression on Tamoxifen /
Aromatase Inhibitors
Anti androgens – FULVESTRANT
Progestins
Other methods
Ovarian Suppression/Ablation :
Medical/Surgical/Radiation Therapy
22. MEGESTROL
The most commonly used second-line hormonal
agents had been progestational drugs, such as
megestrol.
Recent randomized trials have indicated that
fulvestrant or the aromatase inhibitors are equally
effective for palliation of metastatic disease, have less
toxicity, and may provide a survival advantage
compared with megestrol.
23. HORMONAL THERAPY IN
METASTATIC SETTING
BOLERO 2 Trial :
Randomized controlled Phase III trial
Compared everolimus and exemestane versus exemestane and placebo in
hormone-receptor–positive advanced breast cancer who had recurrence or
progression while receiving previous therapy with a nonsteroidal aromatase
inhibitor in the adjuvant setting or to treat advanced disease (or both)
24. Despite the significant improvement seen in progression-free
survival, the addition of everolimus to exemestane did not confer a
statistically significant improvement in overall survvial.
Median overall survival in patients receiving everolimus plus
exemestane was 31.0 months compared to 26.6 months in patients
receiving placebo plus exemestane (HR = 0.89; 95% CI, 0.73–1.10;
log-rank P = .14)
BOLERO 2 TRIAL
25. CIRCULATING TUMOR CELLS
A prospective, multicenter study assessed the role of circulating
tumor cells (CTCs) in predicting survival in 177 patients with
metastatic breast cancer before the start of a new treatment.
Patients with CTC levels greater than five per 7.5 mL of whole blood
had a shorter median progression-free survival time (2.7 vs 7
months; P < .001) and shorter overall survival (10.1 vs > 18
months; P < .001) than did those with fewer than 5 circulating
tumor cells per 7.5 mL of whole blood.
Of all the variables in the statistical model, levels of CTCs at
baseline and at the first follow-up visit were the most significant
predictors of progression-free and overall survival in this group of
patients.
27. CHOICE OF CHEMOTHERAPEUTIC
AGENT
Many patients with recurrent disease will already have had substantial
anthracycline exposure from adjuvant chemotherapy, and retreatment with
doxorubicin or epirubicin is generally avoided.
Taxane-based therapy is often considered for patients with anthracycline-
pretreated breast cancer; however, it is becoming increasingly common for
patients to have received both an anthracycline and a taxane in the adjuvant
setting.
Time to recurrence is also an important consideration. If time to recurrence is
several years following adjuvant therapy, retreatment with prior active agents
may be desirable. If progression or disease recurrence takes place in a
relatively short time (i.e., <12 months), the use of different classes of classes of
agents is generally preferable.
28. Cytotoxic Therapy: Metastatic Breast Cancer
FDA approved drugs before 1994
Methotrexate 1953
Cyclophosphamide 1959
Thiotepa 1959
Vinblastine 1961
5-Fluorouracil 1962
Doxorubicin 1974
29. First-Line MBC
Single-Agent Response Rates
Treatment ORR (%)
Docetaxel1 (75-100 mg/m2) 40-68
Paclitaxel1 (175-250 mg/m2 3-24 h) 32-62
Doxorubicin4 43
Capecitabine3 30
Vinorelbine2 35-53
Gemcitabine2 18-37
Cyclophosphamide4 36
Fluorouracil4 28
Methotrexate4 26
Mitoxantrone4 27
1. Seidman AD, Clin Cancer Res 2.Vogel and Nabholtz. The Oncologist. 1999;4:17.
3. O’Shaughnessy et al. Ann Oncol. 2001;12:1247.4. Sledge. Cancer Control. 1999;6:17.
30.
31. PACLITAXEL IN METASTATIC BREAST CA:
CALGB protocol 9840
577 patients with
metastatic breast cancer who had received one or two prior
regimens were randomized to receive
standard (175 mg/m2) or weekly (80 mg/m2) paclitaxel.
Weekly paclitaxel was shown to be superior with respect to
response rate (40% vs 28%; P = .017), TTP (9 months vs 5 months;
P = .0008), and
overall survival (24 months vs 16 months).
The authors concluded that weekly paclitaxel is superior to
standard paclitaxel in the management of metastatic breast cancer.
Weekly paclitaxel caused more grade 3 sensory/motor neuropathy
and less grade 3 granulocytopenia.
32. DOCETAXEL IN METASTATIC
BREAST CA
Docetaxel has demonstrated overall response rates of
41% in patients with doxorubicin-resistant disease.
It has been shown to be superior to
mitomycin/vinblastine in patients who experienced
disease progression after being treated with an
anthracycline-based chemotherapy regimen.
Docetaxel as a single agent has been shown to produce
objective responses in up to 60% of patients with
metastatic breast cancer that had not previously been
treated with chemotherapy.
35. NAB-PACLITAXEL
The approval in MBC was based on a randomized phase III trial of nab-paclitaxel
260 mg/m2 vs paclitaxel 175 mg/m2 every 3 weeks (q3w).
Significantly less grade 4 neutropenia (9 vs 22%; P < 0.001) and more grade 3
sensory neuropathy (10 vs 2%; P < 0.001) were reported with nab-paclitaxel . Grade 3
sensory neuropathy in patients who received nab-paclitaxel improved to a lower grade
after a median of 22 days of treatment interruption.
Nab-pacli pacli P value HR
ORR 33% 19% 0.001
TTP 23w 17w 0.006 0.75
Median OS 56w 47w 0.024 0.73
36. More 5-FU in the tumour than
healthy tissue with TP-activated
Capecitabine
Schüller J, et al. Cancer Chemother Pharmacol 2000;45:291–7
x3.2*
Tumour tissue
*Ratio of median values
Normal tissue Plasma
5-FU
x21.4*
5-FU
5-FU
5-FU
5-FU
5-FU
5-FU
5-FU
5-FU
5-FU
5-FU5-FU
5-FU 5-FU
5-FU
37. CAPECITABINE Trials in MBC
(Combination Therapy)
Superior survival with capecitabine plus docetaxel combination therapy in
anthracycline-pretreated patients with advanced breast cancer: phase III trial results.
JCO 2002 Jun 15;20(12):2812-23.
PURPOSE:
This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel
therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC.
PATIENTS AND METHODS:
Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily
on days 1 to 14 plus docetaxel 75 mg/m(2) on day 1 (n = 255) or to docetaxel 100 mg/m(2)
on day 1 (n = 256).
38. • Capecitabine + docetaxel reduced the risk of progression and death over
docetaxel alone.
• The overall response rate with Capecitabine plus docetaxel was 32% vs 22% with
docetaxel
alone (P=0.009)
35.7 % reduced risk of progression with
Capecitabine plus Docetaxel over
docetaxel alone.
22.5 % reduced risk of death with
Capecitabine plus Docetaxel over docetaxel
alone.
Capecitabine + Docetaxel (n=255) Capecitabine + Docetaxel (n=255)
CAPECITABINE Trials in MBC
(Combination Therapy)
39. Study design
Primary objective:
• To determine the time to progression
Secondary objective:
• To determine the overall response rate, the
duration of response, the clinical benefit rate
• To evaluate the safety + toxicity
• To assess the quality of life
• To determine the overall survival
Schedule:
Capecitabine 2000 mg/m², days 1 - 14 q 22
A prospective, open label, non randomised phase II trial
CAPECITABINE:MONOTHERAPY IN METASTATIC BREAST CA
40. Median OS, weeks 74.22
95% CIfor median OS (60.59, 87.85)
Median TTP, weeks 31.63
95% CIfor median TTP (26.93, 36.32)
The actual result was a
TTP of 31.63 weeks which
(p<0.05) excludes a TTP
lower than 25 weeks.
Time To Progression, Overall Survival and
Overall Response
Clinical Response N %
CR 13 8.1
PR 29 18
CR+PR 42 26.1
41. Phase III Trial of Ixabepilone + Capecitabine
in MBC Patients Previously Treated/Resistant
to Anthracyclines/Taxanes
Ixabepilone
(40 mg/m2 IV over 3 hr d1 q3wk)
+
Capecitabine
(2000 mg/m2/day PO 2 divided doses
d1-d14 q3wk)
Capecitabine
(2500 mg/m2/day PO 2 divided doses
d1-d14 q3wk)
Metastatic or locally
advanced breast cancer
RESISTANT
to anthracyclines
and taxanes
N = 752
Stratification
Visceral metastases Anthracycline resistance
Prior chemotherapy for MBC Study site
42. Median 95% CI
Ixabepilone +
Capecitabine
5.8 mo (5.5–7.0)
Capecitabine 4.2 mo (3.8–4.5)
Progression-free Survival
by Independent Radiologic Review
HR: 0.75 (0.64–0.88)
P = 0.0003
ProportionProgressionFree
1.0
0.8
0.6
0.4
0.2
0
0 4 8 12 16 20 24 28 32 36
Months
Thomas et al. J Clin Oncol. 2007;25:5210.
44. Summary
Ixabepilone plus capecitabine demonstrates superior efficacy to
capecitabine alone in metastatic breast cancer resistant to anthracyclines
and taxanes
Improvement of PFS (HR 0.75)
2.5-fold increase in ORR (35% vs 14%)
Benefit was consistent across most subgroups
Manageable safety profile (normal or Grade 1 LFTs)
45. GEMCITABINE
In 2004, gemcitabine in combination with paclitaxel was granted RA for the initial
treatment of patients with MBC. The RCT that supported this approval enrolled 529
patients with locally advanced or MBC who had received prior adjuvant or
neoadjuvant anthracycline chemotherapy.17 Patients were randomly assigned to
receive gemcitabine 1,250 mg/m2 on days 1 and 8 with paclitaxel 175 mg/m2 on day
1 or to single-agent paclitaxel 175 mg/m2. Drugs were administered intravenously on
a 21-day cycle.
Approval of gemcitabine was based on an improvement in TTP supported by a
numeric improvement in OS. Median TTP in patients treated with the gemcitabine
plus paclitaxel combination was 5.2 months compared with 2.9 months for paclitaxel
alone (HR, 0.65; 95% CI, 0.52 to 0.81; P < .001). In the final OS analysis, median
survival was 18.6 months in the gemcitabine plus paclitaxel arm and 15.8 months in
the paclitaxel monotherapy arm (HR, 0.86; 95% CI, 0.71 to 1.04).
46. ERIBULIN
In 2010, eribulin was granted RA for the treatment of patients with MBC who have received an
anthracycline, taxane, and at least two chemotherapeutic regimens.
Safety and efficacy were evaluated in an RCT of 762 patients with MBC who had received at least two
chemotherapeutic regimens for the treatment of metastatic disease and experienced disease progression
within 6 months of the last chemotherapeutic regimen.
Patients were randomly assigned in a ratio of two to one to receive eribulin (n = 508) 1.4
mg/m2 intravenously on days 1 and 8 of a 21-day cycle or the physician's choice of a single-agent
therapy selected before randomization (n = 254). Patients had received a median of four prior
chemotherapy regimens in both arms.
Eribulin approval was based on an improvement in OS, with median OS of 13.1 months for eribulin-
treated patients compared with 10.6 months for patients treated in the control arm (HR, 0.81; 95% CI,
0.660 to 0.991; P = .041). The application was also supported by higher ORR in the eribulin treatment
arm (11.2%) compared with the control arm (3.9%) and a consistent, but nonsignificant, effect on PFS
as determined by independent review (median PFS, 113 v 68 days; HR, 0.87; 95% CI, 0.71 to 1.05; P =
.14).
47. The use of combination therapy versus monotherapy or sequential
single agents remains a controversial issue.
Depending on the individual patient and specific treatment goals,
either can be appropriate.
Combination therapies generally result in higher overall
response rates and times to disease progression than with
sequential single agents, but usually at a cost of greater toxicity.
In addition, the higher overall response rates with combination
therapy versus sequential single agents may not necessarily translate
into superior survival outcomes.
COMBINATION VS SEQUENTIAL MONOTHERAPY
48.
49. PARP INHIBITORS
In a randomized phase II study in patients with metastatic triple-
negative breast cancer, O’Shaughnessy et al suggested that iniparib
added to gemcitabine/carboplatin (GC) improved overall survival
without potentiating GC toxicity.
Unfortunately, a subsequent phase III study reported at ASCO in
2011, evaluating the safety and efficacy of GC with or without I in a
similar population with metastatic triple-negative breast cancer,
failed to demostrate a significant improvement in overall survival or
progression-free survival
51. Milestones of HER2/anti-HER2 therapies in BC
EGFR discovery
Cohen
neu oncogene
discovery
Weinberg
EGFR MoAb
inhibited
growth
Mendelsohn
FDA approves
trastuzumab in
adjuvant
setting
1982 19851978 1984 1998 2006 2007 2010
Her2
amplification in
breast cancer
Aaronson
FDA approves
trastuzumab
alone for 2nd
line and in with
paclitaxel for 1st
line MBC
FDA approves
lapatinib +
letrozole for
MBC
FDA approves
lapatinib +
capecitabine
for MBC
1987
Her2/neu
amplification
correlates with
shorter survival
Slamon
MBC : metastatic breast cancer; MoAb : monoclonal antibody
Her2 cloned
Ullrich and
Coussens
1983 2012
FDA approves
pertuzumab +
trastuzumab +
docetaxel for
MBC
2013
FDA approves
trastuzumab
emtansine for
MBC
Accelerated
approval of
pertuuzmab/
trastzumab as
neoadjuvant
therapy
52. TRASTUZUMAB
Trastuzumab received RA in 1998 as a single agent for the
treatment of MBC overexpressing the human epidermal
growth factor receptor 2 (HER2) protein in patients who
have received one or more chemotherapy regimens for
metastatic disease.
The trial supporting the approval was a single-agent SAT
in 222 patients with HER2-overexpressing MBC. Patients
had progressive disease after one (32%) or two (68%)
prior chemotherapy regimens for metastatic
53. Herceptin (Trastuzumab) Study Design
Chemotherapy (AC or Paclitaxel)
Herceptin loading: 4 mg/kg
weekly: 2 mg/kg469
Chemotherapy Alone
Patients with untreated MBC HER2
overexpression 2+ 3+
Slamon et al. N Engl J Med. 2001;344:783.
54. Herceptin :Overall Survival & Progression free
Survival All Patients
PFS 7.4 VS 4.6 m Median OS 25.1 vs 20.3 m
55. CLEOPATRA: Trastuzumab + Docetaxel +
Pertuzumab or Placebo
Baselga J, et al. N Engl J Med. 2012;366(2):109-119.
808 patients
with centrally
confirmed
HER2+ MBC
≥ 6 cycles of docetaxel
recommended
R
A
N
D
O
M
I
Z
E
1:1
Trastuzumab + pertuzumab until
progressive disease
Study dosing every 3 weeks
• Pertuzumab/Placebo: 840 mg loading dose, 420 mg maintenance
• Trastuzumab: 8 mg/kg loading dose, 6 mg/kg maintenance
• Docetaxel: 75 mg/m2, escalating to 100 mg/m2 if tolerated
≥ 6 cycles of docetaxel
recommended
Trastuzumab + placebo until
progressive disease
56. CLEOPATRA: Updated Survival Results
Swain SJ, et al. ESMO 2014. Abstract 350O_PR.
Pertuzumab +
Trastuzumab +
Docetaxel
(n=402)
Placebo +
Trastuzumab +
Docetaxel
(n=406)
P value
Median PFS 18.7 months 12.4 months HR=0.68
P<.0001Improvement: 6.3 months
Median OS 56.5 months 40.8 months HR=0.68
P<.0002Improvement: 15.7 months
PFS = progression-free survival
57.
58.
59.
60. EMILIA: T-DM1 vs Lapatinib + Capecitabine
Verma S, et al. N Engl J Med. 2012;367(19):1783-1791.
T-DM1
Lapatinib +
Capecitabine
P value
Median PFS 9.4 months 6.4 month
HR=.65
P<.0001
Median OS 30.9 months 25.1 months
HR=.682
P=.0006
12-month
survival rate
85.2% 78.4%
24-month
survival rate
64.7% 51.8%
• 991 patients previously treated with trastuzumab and a
taxane
61. LAPATINIB
Lapatinib was granted RA for use in combination with capecitabine for the
treatment of patients with HER2-overexpressing locally advanced or MBC who
have received prior therapy, including anthracyclines, taxanes, and trastuzumab.
An RCT of 399 patients overexpressing HER2 3+ or 2+ supported this approval.
Patients were randomly assigned to receive lapatinib 1,250 mg/m2 orally daily plus
capecitabine 2,000 mg/m2 orally daily for 14 days or single-agent capecitabine
2,500 mg/m2 orally daily for 14 days.
The study was stopped early for efficacy based on a planned interim analysis of
TTP, the primary end point. TTP improvement was statistically significant; median
difference in TTP was 8.5 weeks (HR, 0.57; 95% CI, 0.43 to 0.77; P < .001
At the time of approval, the survival data were not mature, with only 32% of the
planned mortality events. An updated survival analysis after 2 additional years of
follow-up showed no difference in OS (HR, 0.89; 95% CI, 0.71 to 1.10; P = .276).
62. Targeted Therapies for ER+ MBC
CDK 4/6 regulates
cell cycle progression
• Palbociclib is an oral,
potent inhibitor of CDK4/6
• PALOMA-1:
– Palbo + Letrozole is superior
to Letrozole in 1st line ER+
MBC (median PFS 20.2 vs. 10.2
mo, HR 0.49, p=0.0004)
63. BEVACIZUMAB
The initial promising results of a 5-month improvement in
progression-free survival time from the ECOG 2100 trial provided
the basis for the “accelerated approval” of bevacizumab in
metastatic breast cancer by the FDA.
However, given the only modest improverment in progression-
free survival in subsequent trials of bevacizumab and the lack of
improvement in overall survival, coupled with the severe to life-
threatening side effects of bevacizumab, such as gastrointestinal
perforation and severe bleeding, enthusiasm for this agent waned,
and in November 2011 the FDA revoked its accelerated approval
of the breast cancer indication for bevacizumab.
64. BISPHOSPHONATES
Zoledronic acid is an intravenously administered bisphosphonate that reduces
skeletal-related events (SREs) including pain and risk of fracture in women with
breast cancer metastatic to bone. In addition, zoledronic acid treats
hypercalcemia of malignancy.
Multiple published reports have now confirmed the benefit of bisphosphonates
as an adjunct to treatment of patients with bone metastasis. Use of these
agents results in a significant reduction in SREs, including pathologic fracture,
bone pain, and the need for radiation therapy to bone.
Patients with breast carcinoma who had all types of bone were randomized to
receive treatment with either 4 or 8 mg of zoledronic acid as a 15-minute
infusion or 90 mg of pamidronate as a 2-hour infusion every 3 to 4 weeks for
12 months.
The proportion of patients who had an SRE was comparable between treatment
groups (approximately 45%).
However, among patients who had breast carcinoma with at least one
osteolytic lesion, treatment with 4 mg of zoledronic acid was more effective in
reducing skeletal complications than was 90 mg of pamidronate.
65. DENOSUMAB
Denosumab is a fully human monoclonal antibody against receptor
activator of nuclear factor κ B ligand (RANKL), a key mediator of
osteoclast activity.
Results from a phase III pivotal study demonstrated that
denosumab was superior to zoledronic acid in delaying or
preventing SREs in breast cancer patients with bone metastases.
Patients with breast cancer and
66. Systemic Treatment Approach
for Metastatic Breast Cancer
Metastatic Breast Cancer
• Limited metastases (bone & soft tissue)
• Positive hormone receptors
• Hormone responsive
• Disease-free interval 2 years
• Extensive disease or visceral crisis
• Negative hormone receptors
• No response to hormones
Hormonal Therapy Chemotherapy
Response No response No progression Progression of disease
If disease progresses,
second-line hormonal therapy
Second-line chemotherapy