Treatment of breast cancer by Dr.Syed Alam ZebPresentation Transcript
Treatment of breast cancer Dr.Syed Alam Zeb
Carcinoma, NOS (not otherwise specified).
Intraductal (in situ).
Invasive with predominant intraductal component.
Medullary with lymphocytic infiltrate.
Invasive with predominant in situ component.
Paget’s disease, NOS.
Paget’s disease with intraductal carcinoma.
Paget’s disease with invasive ductal carcinoma.
Undifferentiated carcinoma .
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple with no associated invasion of normal breast tissue
Tis (DCIS): Ductal carcinoma in situ
Tis (LCIS): Lobular carcinoma in situ
Tis (Paget's): Paget's disease of the nipple with no tumor. [ Note: Paget's disease associated with a tumor is classified according to the size of the tumor. ]
T1: Tumor ≤2.0 cm in greatest dimension
T1mic: Microinvasion ≤0.1 cm in greatest dimension
T1a: Tumor >0.1 cm but ≤0.5 cm in greatest dimension
T1b: Tumor >0.5 cm but ≤1.0 cm in greatest dimension
T1c: Tumor >1.0 cm but ≤2.0 cm in greatest dimension
T2: Tumor >2.0 cm but ≤5.0 cm in greatest dimension
T3: Tumor >5.0 cm in greatest dimension
T4: Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below
T4a: Extension to chest wall, not including pectoralis muscle
T4b: Edema (including peau d’orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast
T4c: Both T4a and T4b
T4d: Inflammatory carcinoma
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed (e.g., previously removed)
N0: No regional lymph node metastasis
N1: Metastasis to movable ipsilateral axillary lymph node(s)
N2: Metastasis to ipsilateral axillary lymph node(s) fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident lymph node metastasis
N2a: Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures
N2b: Metastasis only in clinically apparent* ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis
N3: Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent* ipsilateral internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or, metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement
N3a: Metastasis in ipsilateral infraclavicular lymph node(s) N3b: Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)
N3c: Metastasis in ipsilateral supraclavicular lymph node(s)
Distant metastasis (M)
MX: Presence of distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
Tis, N0, M0
T1*, N0, M0
T0, N1, M0
T1, N1, M0
T2, N0, M0
T2, N1, M0
T3, N0, M0
T0, N2, M0
T1*, N2, M0
T2, N2, M0
T3, N1, M0
T3, N2, M0
T4, N0, M0
T4, N1, M0
T4, N2, M0
Any T, N3, M0
Any T, Any N, M1
Breast cancer is commonly treated by various combinations of:
Prognosis and selection of therapy may be influenced by:
the age and menopausal status
histologic and nuclear grade of the primary tumor,
estrogen-receptor (ER) and progesterone-receptor (PR) status,
measures of proliferative capacity, and
HER2/neu gene amplification.
Since criteria for menopausal status vary widely, some studies have substituted age older than 50 years as a surrogate for the postmenopausal state.
Patient management following initial suspicion of breast cancer generally includes:
Confirmation of the diagnosis,
Evaluation of stage of disease,
Establishment of unilateral or bilateral disease
Selection of therapy.
Ductal Carcinoma In Situ
Ductal carcinoma in situ (DCIS) is a noninvasive, precancerous condition.
DCIS can progress to become invasive cancer, but estimates of the likelihood of this vary widely.
DCIS accounts for about 18% of all newly diagnosed invasive plus noninvasive breast tumors in the United States.
Very few cases of DCIS present as a palpable mass; 80% are diagnosed by mammography alone
Treatment options for DCIS
Total mastectomy with or without tamoxifen.
Breast-conserving surgery and radiation therapy, with or without tamoxifen.
Breast-conserving surgery without radiation therapy. A large national clinical trial comparing breast-conserving surgery and tamoxifen with or without radiation therapy is currently under way
Lobular Carcinoma In Situ
Strictly speaking, it is not known to be a premalignant lesion, but rather a marker that identifies women at an increased risk for subsequent development of invasive breast cancer. This risk remains elevated even beyond 2 decades, and most of the subsequent cancers are ductal rather than lobular.
LCIS is usually multicentric and is frequently bilateral.
Treatment of Lobular Carcinoma In Situ
Most women with LCIS can be managed without additional local therapy after biopsy.
No evidence is available that re-excision to obtain clear margins is required.
Tamoxifen has decreased the risk of developing breast cancer in women with LCIS and should be considered in the routine management of these women
Bilateral prophylactic mastectomy is sometimes considered an alternative approach for women at high risk for breast cancer.
Axillary lymph node dissection is not necessary.
Treatment options for patients with LCIS
Observation after diagnostic biopsy.
Tamoxifen to decrease the incidence of subsequent breast cancers.
Ongoing breast cancer prevention trials.
Bilateral prophylactic total mastectomy, without axillary node dissection.
Management of Stage I, II, IIIA, and Operable IIIC Breast Cancer
After the presence of a malignancy is confirmed and histology is determined, treatment options should be discussed with the patient before a therapeutic procedure is selected.
The surgeon may proceed with a definitive procedure
Estrogen-receptor (ER) and progesterone-receptor (PR) status should be determined for the primary tumor.Additional pathologic characteristics, including grade, proliferative activity, and human epidermal growth factor receptor 2 (HER2/neu) status, may also be of value.
Options for surgical management of the primary tumor include:
breast-conserving surgery plus radiation therapy,
mastectomy plus reconstruction, and
Selection of a local therapeutic approach depends on:
the location of the lesion
size of the lesion
analysis of the mammogram
breast size, and
the patient’s attitude toward preserving the breast.
relative contraindications to breast-conserving therapy
The presence of multifocal disease in the breast
history of collagen vascular disease.
A patient’s age should not be a determining factor in the selection of breast-conserving treatment versus mastectomy
Whether young women with germ-line mutations or strong family histories are good candidates for breast-conserving therapy is not certain.
surgical techniques used include:
Patients whose tumors have these characteristics
may benefit from a more generous initial excision
to avoid the need for a re-excision:
1. large tumors (T2 lesions),
2. positive axillary nodes,
3. extensive intraductal component,
4. palpable tumors, and
5. lobular histology
Dealing with axillary lymph nodes
Axillary node dissection even in the presence of clinically negative nodes is a necessary staging procedure.
Controversy exists as to the extent of the procedure because of long-term morbidity
The standard evaluation usually involves only a level I and II dissection, thereby removing a satisfactory number of nodes for evaluation (i.e., 6-10 at a minimum), while reducing morbidity from the procedure.
Sentinel lymph node biopsy
The SLN is defined as the first node in the lymphatic basin that receives primary lymphatic flow.
Studies have shown that the injection of technetium-labeled sulfur colloid, vital blue dye, or both around the tumor or biopsy cavity, or in the subareolar area, and subsequent drainage of these compounds to the axilla results in the identification of the SLN in 92% to 98% of patients
These reports demonstrate a 97.5% to 100% concordance between SLN biopsy and complete axillary lymph node dissection
The results of a randomized trial of 532 patients with T1 carcinomas undergoing either SLN biopsy plus complete axillary dissection or SLN biopsy alone showed no axillary recurrences in either group and no difference in the 3-year disease-free survival
The reported false-negative rates (i.e., the number of patients with negative SLN biopsy divided by the number of patients with positive axillary nodes at the time of axillary node dissection) of SLN biopsy range from 0% to 10%.
Following Breast conservation
Radiation therapy following Breast conservation
Postoperative external-beam radiation therapy to the entire breast with doses of 45 Gy to 50 Gy, in 1.8 Gy to 2.0 Gy daily fractions over a 5-week period.
A further radiation boost is commonly given to the tumor bed. Two randomized trials conducted in Europe have shown that using boosts of 10 Gy to 16 Gy reduces the risk of local recurrence from 4.6% to 3.6% at 3 years ( P = .044),[and from 7.3% to 4.3% at 5 years ( P < .0001), respectively
If a boost is used, it can be delivered either by external-beam radiation therapy,or by using an interstitial radioactive implant.
Radiation therapy following mastectomy
Postoperative chest wall and regional lymph node adjuvant irradiation is given to selected patients considered at high risk for local-regional failure following mastectomy:
Those with 4 or more positive axillary nodes
Grossly evident extracapsular nodal extension
Large primary tumors, and
Very close or positive deep margins of resection of the primary tumor.
Patients with 1 to 3 involved nodes without any of the previously noted risk factors are at low risk of local recurrence, and the value of routine use of adjuvant radiation therapy is unclear.
The benefit of tamoxifen was found to be restricted to women with ER-positive or ER-unknown breast tumors. In these women, the 15-year absolute reductions in recurrence and mortality associated with 5 years of use are 12% and 9%, respectively.
Women younger than 50 years obtained a degree of benefit from 5 years of tamoxifen similar to that obtained by older women.
In addition, the proportional reductions in both recurrence and mortality associated with tamoxifen use were similar in women with either node-negative or node-positive breast cancer, but the absolute improvement in survival at 10 years was greater in the latter group (5.3% vs. 12.5% with 5 years of use)
The current recommendation is that adjuvant tamoxifen be discontinued after 5 years in all patients as current standard therapy.
Tamoxifen toxic effects
Increased incidence of deep venous thrombosis and pulmonary emboli.
Benign ovarian cysts
Aromatase inhibitors: anastrozole
Patients on anastrozole have a significantly longer disease-free survival than those on tamoxifen.
Aromatase inhibitors: exemestane
Better disease free survival
Women on exemestane had significantly more visual disturbances, arthralgia, diarrhea, and osteoporosis, but women on tamoxifen had significantly more gynecologic symptoms, muscle cramps, vaginal bleeding, thromboembolic disease, and second malignancies other than breast cancer.
No difference was observed in overall survival
Aromatase inhibitors: letrozole
Better disease free survival
Significantly more hot flashes, arthritis, arthralgia and myalgia, but less vaginal bleeding. New diagnoses of osteoporosis were more frequent on letrozole
Improvement in overall survival
Surgery, radiation therapy or ovarian suppression with LHRH agonists
Ovarian suppression or ablation reduced the absolute risk of recurrence at 15 years by 4.3% and the risk of death from breast cancer by 3.2.
Duration of CMF-based chemotherapy
No survival benefit was demonstrated for durations greater than 6 months.
Anthracycline based chemotharapy
Slight advantage for the anthracycline regimens in both premenopausal and postmenopausal patients. Uncertainty remains, however, about whether there is an advantage to combining both regimens.
Evidence suggests that particular tumor characteristics may predict anthracycline-responsiveness. Data from retrospective analyses of randomized clinical trials suggest that, in patients with node-positive breast cancer, the benefit is restricted to those patients whose tumors overexpress HER2/neu. The routine use of HER2/neu to select those patients that should or should not receive anthracycline-containing regimens should await further confirmation
Role of Preoperative adjuvant chemotherapy
Preoperative chemotherapy may be beneficial in women who desire breast conservation surgery but who would otherwise not be considered candidates because of the size of their tumor.
Three clinical trials addressing the role of the anti-HER2/neu antibody, trastuzumab, as adjuvant therapy for patients with HER2 overexpressing cancers released the results of interim analyses.
Highly significant improvement in disease-free survival and overall survival
Risk Categories for Women With Node-Negative Breast Cancer Low risk (has all listed factors) Intermediate risk High risk (has at least 1 listed factor) Tumor size ≤ 1cm 1-2 cm >2 cm ER or PR Status positive positive negative Tumor grade Grade 1 grade 1-2 grade 2-3
Adjuvant systemic treatment for node negative premenopausal women Patient group Low risk Intermediate risk High risk ER-positive or PR-positive None or tamoxifen 1.T ± C 2.Ov Ab 3.GnRH analog
C & T
C & Ov Ab/ GnRH analog
C & T & Ov Ab/ GnRH analog
4.Ov ab ± T
ER-negative or PR-negative — — Chemotherapy
Adjuvant systemic treatment for node negative postmenopausal women Patient group Low risk Intermediate risk High risk ER-positive or PR-positive None or tamoxifen T ± C T ± C ER-negative or PR-negative — — Chemotherapy Older than 70 years None or tamoxifen T ± C T. Consider chemotherapy if ER-negative or PR-negative
Adjuvant systemic treatment for node positive premenopausal women Patient group Treatments ER or PR-positive
C & T
C & Ov Ab/ GnRH analog
C & T & Ov Ab/ GnRH analog
4. Ov ab ± T
5. GnRH ±T
ER-negative or PR-negative Chemotherapy
Adjuvant systemic treatment for node positive postmenopausal women Patient group Treatments ER or PR-positive T ± C ER-negative or PR-negative Chemotherapy Older than 70 years Tamoxifen alone; consider chemotherapy if receptor-negative
Candidates for whom adjuvant therapy may not be necessary
Individuals with small primary tumors (<1 cm) and negative axillary nodes who have an excellent prognosis, with nearly 90% of patients alive and free of disease at 20 years in one series.
Proposals have been made to treat elderly patients with tamoxifen alone and without surgery. This approach has unacceptably high local failure rates and, outside of a clinical trial setting, should be used only for patients who are not candidates for mastectomy or breast-conserving surgery plus radiation therapy, or for those who refuse these options.
Inoperable stage IIIB or IIIC or inflammatory breast cancer
Multimodality therapy delivered with curative intent is the standard of care for patients with clinical stage IIIB disease.
32% of patients with ipsilateral supraclavicular node involvement and no evidence of distant metastases (pN3c) can have prolonged disease-free survival at 10 years with combined modality therapy.This result suggests such patients should be treated with the same intent.
Initial surgery is generally limited to biopsy to permit the determination of histology, ER and PR levels, and HER2/neu overexpression.
Initial treatment with anthracycline-based chemotherapy and/or taxane-based therapy is standard.
For patients who respond to neoadjuvant chemotherapy, local therapy may consist of total mastectomy with axillary lymph node dissection followed by postoperative radiation therapy to the chest wall and regional lymphatics. Breast-conserving therapy can be considered in patients with a good partial or complete response to neoadjuvant chemotherapy. Subsequent systemic therapy may consist of further chemotherapy.
Hormone therapy should be administered to patients whose tumors are ER-positive or unknown.
Stage IV breast cancer
Treatment of metastatic breast cancer will usually involve hormone therapy and/or chemotherapy with or without trastuzumab (Herceptin). Radiation therapy and/or surgery may be indicated for patients with limited symptomatic metastases. Fungating tumours
Bisphosphonates to reduce skeletal morbidity in patients with bone metastases
Stage IV breast cancer (cont)
Hormone therapy as initial treatment for a postmenopausal patient with newly diagnosed metastatic disease if the patient’s tumor is ER-positive, PR-positive, or ER/PR-unknown. Hormone therapy is especially indicated if the patient’s disease involves only bone and soft tissue and the patient has either not received adjuvant antiestrogen therapy or has been off such therapy for more than 1 year.
Women whose tumors are ER-positive or unknown, with bone or soft tissue metastases only, who have received an antiestrogen within the past year should be given second-line hormone therapy. Examples of second-line hormone therapy in postmenopausal women include selective aromatase inhibitors, such as anastrozole, letrozole, or exemestane; megestrol acetate; estrogens; androgens; and the ER down-regulator, fulvestrant.[
Stage IV breast cancer (cont)
Premenopausal women should undergo oophorectomy (surgically, with external-beam radiation therapy or with an LHRH agonist).
Patients with lymphangitic pulmonary metastases, major liver involvement, and/or central nervous system involvement should not receive hormone therapy as a single modality. Patients with structural compromise of weight-bearing bones should be considered for surgical intervention and/or radiation in addition to systemic therapy. Patients with vertebral body involvement should be evaluated for impending cord compression even in the absence of neurologic symptoms. Increasing bone pain and increasing alkaline phosphatase within the first several weeks of hormone therapy does not necessarily imply disease
Patients whose tumors have progressed on hormone therapy are candidates for cytotoxic chemotherapy. Patients with hormone receptor-negative tumors and those with visceral metastases are also candidates for cytotoxic agents.
Evidence from randomized trials that periodic follow-up with bone scans, liver sonography, chest x-rays, and blood tests of liver function does not improve survival or quality of life when compared to routine physical examinations.Even when these tests permit earlier detection of recurrent disease, patient survival is unaffected.
Based on these data, some investigators recommend that acceptable follow-up be limited to physical examination and annual mammography for asymptomatic patients who complete treatment for stage I to stage III breast cancer.