Staging and Examination Most stage III invasive breast cancers are evaluated at a stage similar to that of T3N1M0. Bilateral mammograms and breast ultrasound are mandatory. Genetic counseling is recommended for patients at high risk for hereditary breast cancer. Other tests are optional unless there are immediate symptoms or other abnormalities, such as breast MRI, bone scan (category 2B), diagnostic CT or MRI of the abdomen (category 2A), and PET/CT scan is an optional extra (category 2B). When CT or MRI cannot be performed, ultrasound may be an alternative. The panel believes that FDG PET/CT is most helpful for suspicious imaging findings. However, the role of FDG PET/CT for lymph nodes and distant metastases is supported by only a few studies. Retrospective studies have shown high concordance (81%) between bone scan and FDG PET/CT for the diagnosis of suspected bone metastases in stage I-III breast cancer. The panel concluded that bone scan may not be performed if FDG PET/CT is positive for bone metastases. Suspicious sites on PET/CT scan should be confirmed by biopsy if possible if there are implications for treatment. It is important to understand the difference between PET/CT and adequately optimized CT; PET/CT focuses on PET imaging, whereas adequately optimized CT is used as a stand-alone diagnostic CT exam. Understanding this will help in the development of PET/CT and diagnostic CT. Locally advanced breast cancer that is operable (clinical stage T3N1M0) Locally advanced breast cancer is a subtype of invasive breast cancer in which clinical and imaging evaluation shows disease progression limited to the breast and regional lymph nodes. The AJCC clinical staging system, which classifies locally advanced breast cancer as stage III, is recommended for determining whether to operate. For patients with stage IIIA breast cancer who are not receiving neoadjuvant chemotherapy, the postoperative systemic adjuvant regimen is similar to that for patients with stage II breast cancer. For patients with inoperable, non-inflammatory locally advanced breast cancer, the standard of care is initial preoperative anthracycline-based systemic therapy (with or without paclitaxel). The initial chemotherapy for patients with HER-2 positive locally advanced breast cancer should include preoperative chemotherapy with trastuzumab. Local treatment after clinical response to preoperative chemotherapy includes: total mastectomy with level I/II axillary lymph node dissection with or without second-stage breast reconstruction; or tumor resection with level I/II axillary lymph node dissection. Both local treatments carry a high risk of local recurrence, necessitating the use of chest wall (or breast) and supraclavicular lymph node radiation therapy. If the internal breast lymph nodes are involved, they should also be treated with radiotherapy. If no internal breast lymph node metastases are found, the internal breast area may be considered for inclusion in the irradiation (category 2B). Adjuvant therapy includes completion of the planned course of chemotherapy (if not completed prior to surgery) and endocrine therapy for hormone receptor-positive patients. If HER-2 positive, trastuzumab therapy should be completed for up to 1 year (Category 1). Endocrine therapy and trastuzumab therapy may be used in conjunction with radiation therapy if indicated. Non-operable stage III breast cancer that has progressed during preoperative chemotherapy may be treated with palliative breast radiotherapy to enhance local control. For all subgroups of such patients, the standard treatment regimen should be local therapy followed by systemic adjuvant chemotherapy. Hormone receptor-positive patients should be treated with tamoxifen (or an aromatase inhibitor if postmenopausal); HER-2-positive patients should be treated with trastuzumab. post-treatment follow-up for patients with stage III breast cancer is the same as for patients with early invasive breast cancer. Post-treatment monitoring and follow-up Post-treatment follow-up is best performed by a member of the treatment team, and regular physical examinations should be performed every 4-6 months for the first 5 years after treatment and annually thereafter. Mammograms should be performed annually. Routine alkaline phosphatase and liver function tests are not included in the guidelines. In addition, the panel noted that there is no evidence to support the use of “tumor markers” and that routine bone scans, CT, MRI, PET, and ultrasound are not recommended for asymptomatic patients given that they do not provide a survival benefit or slow disease recurrence. Breast-specific MRI may be considered for post-treatment surveillance and follow-up in patients at high risk of bilateral disease, such as BRCA1/2 mutation carriers, who have a higher rate of contralateral breast cancer recurrence after breast-conserving surgery or total mastectomy compared to patients with disseminated breast cancer. Because tamoxifen in postmenopausal patients is associated with endometrial cancer, the panel recommends that female patients with an intact uterus should undergo annual gynecologic examinations while on tamoxifen therapy and be promptly evaluated for any small amount of vaginal bleeding. Routine endometrial biopsy or ultrasonography in asymptomatic female patients is not recommended. Neither of these 2 tests has been shown to be an effective screening tool in any group of women. The vast majority of patients with tamoxifen-associated endometrial cancer present with small amounts of early vaginal bleeding. If aromatase inhibitors are considered in patients with post-treatment amenorrhea, basal levels of estradiol and gonadotropins should be measured and monitored continuously before starting aromatase inhibitor therapy. Bilateral adnexal resection ensures that young women with post-treatment amenorrhea are in menopausal status and may be considered in young patients prior to initiating aromatase inhibitor therapy. For patients on adjuvant endocrine therapy, symptomatic treatment of hot flashes and depression is often required. Venlafaxine is effective in reducing hot flashes. Tamoxifen in combination with SSRIs such as paroxetine or fluoxetine can reduce plasma levels of endoxifen, an active metabolite of tamoxifen. However, the SSRIs citalopram, etanercept, fluvoxamine, gabapentin, sertraline, and venlafaxine had minimal or no effect on the metabolism of tamoxifen. Follow-up also included assessment of patient adherence to current therapy (e.g., endocrine therapy). Predictors of poor adherence include treatment-related adverse effects, and patients’ incomplete understanding of the benefits of regular medication use. The panel recommends a concise approach to improving patient adherence, such as direct questioning at each follow-up visit, and a concise explanation of the significance of regular medication use and the importance of long-term endocrine therapy. There is evidence that a healthy lifestyle leads to a better prognosis for breast cancer. A case-control study showed that obesity (BMI ≥ 30), smoking and alcohol consumption were associated with contralateral breast cancer. A prospective study showed that eating more fruits and vegetables and physical activity were associated with improved survival. Therefore, the panel recommends that one should adopt an active lifestyle and maintain an ideal weight (BMI 20-25). Many young women treated for breast cancer still maintain or will revert to premenopausal status. For these women, the panel opposes the use of hormonal contraception, regardless of the hormone receptor status of the tumor. Other contraceptive methods are recommended, including intrauterine devices, barrier methods, and tubal ligation or spousal vasectomy (for patients with no future desire to have children). The panel does not recommend breastfeeding during endocrine therapy or chemotherapy. Breastfeeding after breast-conserving therapy is not contraindicated; however, the breast may fail to lactate or produce decreased milk after radiation therapy. The panel recommends skeletal monitoring with basal bone mineral density testing and subsequent periodic checkups for women on adjuvant aromatase inhibitor therapy or secondary to ovarian failure after treatment. The use of estrogens, progestins, and selective estrogen receptor modulators for the treatment of osteoporosis or osteopenia in breast cancer patients is opposed. Bisphosphonate drugs are usually preferred. For the duration of anti-osteoporosis treatment, factors to consider include bone mineral density, efficacy, and the risk of continued bone loss or fracture. Dental examinations should be performed prior to bisphosphonate medication, and calcium and vitamin D supplements should be administered at the time of treatment.