You may consider answering the following multiple choice questions before reading the information provided. The answers are given at the bottom of the page.
Q1: Which of the following statements is correct regarding treatment of early stage breast cancer?
1. Mastectomy has shown a better survival compared with breast conservative surgery and radiation therapy.
2. Adjuvant hormone therapy in ER/PR negative breast cancer reduces the risk of recurrence.
3. Axillary lymph node assessment is important to guide adjuvant therapy.
4. Adjuvant trastuzumab reduces breast cancer mortality irrespective of tumor HER2 protein status.
Q2: All of the following statements regarding local treatment of early stage breast cancer are correct except?
1. Mastectomy is the surgery of choice for multi-centric breast cancer.
2. Post-mastectomy chest wall irradiation in women with large tumor size or multiple involved lymph nodes reduces the risk of recurrence.
3. Previous radiation therapy to the breast is not a contraindication to breast conservative approach.
4. Sentinel lymph node biopsy is an alternative to axillary node dissection in women with a clinically negative axilla.
Q3: Which of the following statement is correct regarding systemic treatment of early stage breast cancer?
1. Aromatase inhibitors are standard adjuvant hormone therapy in premenopausal women.
2. Adjuvant chemotherapy is beneficial only in ER/PR negative breast cancer.
3. More than 80 percent of breast cancers overexpress HER2 protein and can be treated with trastuzumab.
4. Adjuvant chemotherapy benefits both premenopausal and postmenopausal women.
Q4: All of the following statements regarding treatment of early stage breast cancer are correct except?
1. Tumor size, status of the axillary lymph nodes, hormone receptors status and the protein HER2 over-expression are important factors that influence the treatment of early stage breast cancer.
2. Neoadjuvant therapy is given after a definitive local treatment to treat microscopic disease.
3. Trastuzumab has been associated with an increase in the incidence of cardiac dysfunction.
4. Radiation therapy is a standard component of breast conserving therapy.
TREATMENT OPTIONS FOR EARLY STAGE INVASIVE BREAST CANCER
· Breast cancer is the most common female cancer in the North America, the second most common cause of cancer death in women.
· Early stage breast cancer is confined to the loco-regional lymph nodes and or breast with no evidence of distant metastases.
· The primary treatment of early stage invasive breast cancer is comprised of definite local treatment to remove the primary tumor and adjuvant local or systemic therapy to treat microscopic residual disease.
· Adjuvant therapy reduces the risk of recurrence and cancer-related mortality.
· A variety of factors influence the treatment of localized breast cancer including woman's age, menopausal status, tumor size, status of the axillary lymph nodes, and whether the tumor expresses hormone receptors and/or the protein HER2.
Primary Tumor Management
· Surgery (mastectomy or breast conserving surgery) is the main component of curative therapy for breast cancer.
· Multiple randomized controlled trials provide evidence for the equivalency of mastectomy and breast conservative surgery plus radiation therapy in women with early stage breast cancer.
· Patients with large tumors that cannot be treated by breast conservative approach are best treated by mastectomy.
· Preoperative systemic therapy (chemotherapy or hormone therapy if hormone receptor positive) followed by surgery is an alternative approach for these patients in an effort to make breast conservation possible.
Contraindication to Breast Conservative Treatment
· Persistently positive resection margins after multiple reexcision.
· Multicentric disease involving separate breast quadrants.
· Diffuse malignant-appearing mammographic microcalcifications, suggestive of multicentric disease.
· Prior radiation to the breast.
· Pregnancy (it may be possible to perform breast-conserving surgery in the third trimester and deferring breast radiation therapy until after delivery).
Breast Reconstruction Surgery
· Breast reconstruction can be performed following mastectomy.
· There are two general reconstructive options: implants and autogenous tissue reconstruction.
· Both types of procedures may be performed at the time of the primary breast cancer surgery, or deferred till completion of adjuvant therapy.
Management of the Regional Lymph Node
· Axillary node status is an important prognostic factor.
· For most women with early breast cancer, surgical assessment of axillary nodal status is required to guide decisions on further therapy.
· Increasingly, the status of the axillary nodes is being assessed by sentinel lymph node biopsy (SLNB), which is associated with a lower rate of morbidity than full axillary lymph node dissection.
· Guidelines from the American Society of Clinical Oncology (ASCO) recommend SLNB as an alternative to axillary node dissection in women with a clinically negative axilla.
Breast Radiation After Lumpectomy
· Radiation therapy (RT) with a boost to the lumpectomy cavity is considered a standard component of breast conserving therapy and may also be indicated after mastectomy.
· The purpose of radiation is to eradicate subclinical residual disease and minimize local recurrence rates.
Postmastectomy Chest Wall Radiation
· Postmastectomy chest wall irradiation in women with high-risk disease (ie, large tumor size or involved lymph nodes) reduces the risk of locoregional recurrence, and mortality from breast cancer.
ADJUVANT SYSTEMIC THERAPY
· Adjuvant systemic therapy refers to the administration of hormone therapy, chemotherapy and/or trastuzumab (a humanized monoclonal antibody directed against HER2) after definitive local therapy for breast cancer.
· The aim of systemic adjuvant therapy for early stage cancer following curative surgery is to treat micrometastases thereby reduces risk of recurrence and cancer-related mortality.
· The choice of hormone therapy, chemotherapy, and trastuzumab depends upon both clinicopathologic factors (eg, presence or absence of nodal metastases, tumor size) as well as biologic/molecular factors (eg estrogen and progesterone receptor (ER/PR) status and HER2 overexpression).
· Adjuvant systemic therapy benefits the majority of women with early stage breast cancer, but the magnitude of benefit is greatest for women with high risk disease.
Hormone Therapy
· Adjuvant hormone therapy in women with ER/PR positive early-stage breast cancer reduces the risk of recurrence and mortality.
· ER and PR negative breast cancers do not respond to hormone therapy. Therefore, adjuvant hormone therapy is not indicated in ER/PR negative breast cancer.
· In women with operable ER/PR positive tumors, 5 years of tamoxifen reduces the risk of recurrence on average by 41% and breast cancer mortality by 34%.
· For premenopausal women, 5 years of tamoxifen is the standard adjuvant hormone therapy. The suppression of ovarian function is another effective therapeutic option in these women.
· In postmenopausal women, third-generation aromatase inhibitors (e.g. anastrozole, letrozole, exemestane), are superior to 5 years of adjuvant tamoxifen. In such women, use of aromatase inhibitors is recommended at some point in the adjuvant hormone treatment.
· Aromatase inhibitors are not indicated in premenopausal women.
Chemotherapy
· Adjuvant chemotherapy benefits both premenopausal and postmenopausal women irrespective of hormone receptors status, although the absolute magnitude of benefit is greater in younger as compared to older women and in ER/PR negative than ER/PR positive breast cancer.
· According to Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview analysis adjuvant chemotherapy in women younger than 50 reduces the risk of disease relapse and death by 37 and 30 percent, respectively. This translated into a 10 percent absolute improvement in 15-year survival (42 versus 32 percent).
· For women aged 50 to 69, the risk of relapse or death decreases by 19 and 12 percent, respectively. This translated into a 3 percent absolute gain in 15-year survival (50 versus 47 percent).
· For women aged 70 years and older, the benefit of chemotherapy is uncertain because few studies included women in this age group.
· Some women undergo chemotherapy prior to definitive local treatment, a situation referred to as neoadjuvant therapy. Although this approach is more common in women with locally advanced or inflammatory breast cancer it may consider to facilitate breast conservative surgery.
· Combination chemotherapy is the adjuvant treatment of choice for women with hormone non-responsive (ie, ER/PR negative) breast cancer who need adjuvant therapy. It is also appropriate for women with high risk ER positive breast cancer, in conjunction with hormone therapy.
· Anthracycline and taxane-based chemotherapy regimens are commonly used in this setting.
Trastuzumab (Herceptin®)
· Approximately 20 percent of breast cancers overexpress the HER2 protein.
· Early data from several randomized trials suggest that the addition of trastuzumab to anthracycline and taxane-containing adjuvant chemotherapy regimens provides substantial benefit for women with HER2-positive breast cancer, both in terms of disease recurrence and overall survival.
· Trastuzumab is recommended in addition to an anthracycline and taxane-based regimen for women with HER2-overexpressing, node-positive breast cancer, and possibly for those with high-risk, node-negative disease.
· It has been associated with an increase in the incidence of both symptomatic as well as asymptomatic cardiac dysfunction.
Multiple choice question answers:
Q1: Answer: 3
Q2: Answer: 3
Q3: Answer: 4
Q4: Answer: 2
