Approximately 25% of breast cancers overexpress the HER2 cell surface signal-transduction protein. Patients with HER2-positive breast cancer experience a higher risk of recurrence compared to patients with HER2-negative breast cancer (without treatment with trastuzumab). Trastuzumab is a humanized monoclonal antibody designed to target HER2-positive cancer cells. When given in conjunction with adjuvant chemotherapy, trastuzumab reduces the relative risk of recurrence and death by 50% and 33%, respectively. Professional organizations recommend administering trastuzumab for patients with HER2-positive node-positive cancer or node-negative cancer measuring >1 cm. Approximately 2–3% of patients who receive trastuzumab develop symptomatic congestive heart failure. Consequently, this medication is contraindicated in patients with preexisting heart failure. For patients who receive trastuzumab, monitoring of left ventricular ejection fraction periodically throughout treatment is recommended.

STAGE IV BREAST CANCER (METASTATIC)

Approximately 10–20% of women diagnosed with breast cancer have stage IV (metastatic) disease at initial presentation, and approximately 20% of women diagnosed with nonmetastatic breast cancer eventually develop recurrent metastatic disease. Common sites of metastatic breast cancer include the bone, distant lymph nodes, lungs, liver, pleura, and brain. The diagnosis is confirmed through the biopsy of a suspicious mass. Occasionally, a confirmatory biopsy is not performed if the clinical scenario is fully consistent with metastatic breast cancer and/or the suspicious mass is not easily accessible to biopsy. Metastatic breast cancer is not curable. The median survival is approximately 2 to 2.5 years. A small fraction of patients, perhaps 5–10%, survive 5 or more years. Women are likely to experience a slower rate of cancer progression and a better survival if they have a hormone-receptor–positive or low-grade cancer, are more fit (have a good performance status), have fewer sites of metastatic disease, have little visceral organ involvement, or if there was a long interval between their original cancer diagnosis and recurrence. The primary goal of therapy for patients with metastatic breast cancer is to maximize quality of life by reducing or preventing symptoms caused by the cancer without precipitating therapy-related side effects. Studies suggest that systemic treatments (chemotherapy and/or hormonal therapy) may also prolong survival, although survival benefits are likely modest.

    The initial management of hormone-receptor–positive metastatic breast cancer most commonly involves the administration of an anti-estrogen medication. Approximately 75% of cancers respond to initial hormonal therapy. Hormonal treatment options include tamoxifen with or without a gonadotropin-releasing hormone agonist for premenopausal women and a selective aromatase inhibitor (e.g., anastrozole, letrozole or exemestane) for postmenopausal women. The initial management of hormone-receptor–negative metastatic breast cancer typically involves the administration of systemic chemotherapy. Chemotherapy is also a reasonable treatment option for any woman who has extensive or symptomatic metastatic disease, regardless of the cancer’s hormone-receptor status. Approximately 50–75% of cancers experience clinical benefit from initial chemotherapy (i.e., the cancer shrinks or remains stable). A number of chemotherapy medications and several targeted therapies have been approved to treat metastatic breast cancer. Trastuzumab, a monoclonal antibody, targets the HER2 receptor so it can only be used to treat women with HER2-positive breast cancer. When used in combination with chemotherapy, trastuzumab improves overall survival by approximately 5 months. Much of the current research into breast cancer treatments involves the development of new targeted therapies. A number of relatively new therapies target the HER2 receptor, including lapatinib, pertuzumab, and ado-trastuzumab emtansine. Lapatinib, for example, when given together with the chemotherapy medication capecitabine, improves time to tumor progression by approximately 4 months. Other targeted therapies currently under development include inhibitors of the PI3 kinase signal transduction pathway. Once started, a systemic treatment is usually continued until the cancer grows/progresses or the patient experiences intolerable side effects.

    Targeted local therapies such as surgical excision, radiation therapy, or radio-frequency ablation are sometimes indicated to palliate symptomatic metastatic deposits. Treating pain, anxiety, depression, and other symptoms commonly experienced by women with metastatic breast cancer is an integral aspect of cancer care as well. For women who have metastatic bony deposits, the regular administration of an intravenous bisphosphonate (e.g., pamidronate or zoledronic acid) or the subcutaneous medication denosumab (a receptor activator of nuclear factor kappa-B ligand [RANK] ligand inhibitor) helps prevent/delay the development of skeletal complications and palliates bone pain. Finally, providing optimal palliative care often requires the collaboration of multiple specialists including the oncologist, psychiatrist, social worker, and the hospice service.

SUMMARY OF BREAST CANCER TREATMENT

With nonmetastatic breast cancer (stages 0–III; see table 10.4), cure is the goal of therapy, and surgery is the primary treatment used to achieve this goal. Even with optimal surgical resection, there is still a risk that breast cancer can recur. Radiation therapy (to the breast, chest wall and/or surrounding lymph nodes) is sometimes used to reduce the risk of local recurrence, and medications (anti-estrogen, HER2-directed and/or cytotoxic chemotherapy) are sometimes used to reduce the risk of local (breast and ipsilateral axillary lymph nodes) and distant (beyond the breast and local lymph nodes) recurrence. Reducing the risk of recurrence helps increase the chance of cure. The major factors that providers consider when deciding which treatments to recommend and how to sequence the therapies include stage, biological subtype (hormone receptor status, HER-2 status, and grade), age, menopausal status, comorbid medical conditions/general health, and patient preference. After completing definitive therapy for nonmetastatic breast cancer, the only surveillance study recommended routinely is mammography to the remaining breast tissue; other radiologic scans and laboratory studies to screen for distant recurrence in asymptomatic women are not recommended. Metastatic breast cancer (either stage IV at diagnosis or distant recurrence some time after diagnosis of an earlier-stage breast cancer) is not curable. The goals of therapy are to reduce/alleviate symptoms from cancer and possibly prolong survival. Treatment usually involves medications; surgery and radiation are sometimes used to help control symptoms.

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