Cancer Control

Hereditary predisposition to breast and ovarian cancer, most commonly due to germline mutations in BRCA1 and BRCA2, has been recognized for many years. The optimal clinical management of individuals with such a predisposition is not yet completely defined.

The current literature regarding the clinical management of individuals at risk for hereditary breast and ovarian cancer was reviewed.

Women with germline BRCA1 or BRCA2 mutations are at substantially increased risk for breast and ovarian cancer, although the risks may not be as high as originally reported. Current surveillance options are restricted in their effectiveness by both host and tumor factors as well as limitations of the techniques. Surgical prevention options, while effective, may be complicated by physical or psychological morbidity. Nonsurgical prevention options are under development.

The ability to define women as being at hereditary risk for breast and ovarian cancer facilitates the use of specialized surveillance and prevention strategies. Genetic testing, which plays a role in defining risk, requires careful pre- and post-test counseling to discuss the limitations of testing itself and available management strategies.

The majority of women diagnosed with early-stage breast cancer have an excellent long-term prognosis, but many will undergo temporary or permanent chemotherapy-induced amenorrhea.

While breast cancer is more common in older women, about 1 in 200 women under the age of 40 is at risk to develop breast cancer. Many of these women benefit from chemotherapy but are afraid to risk the opportunity to bear children. The authors review the current studies on the impact of adjuvant chemotherapy on amenorrhea and fertility in women with breast cancer.

The likelihood of amenorrhea is based on the specific adjuvant chemotherapy regimen administered and the age of the patient. Future childbirth is a viable option for women treated for breast cancer at an early stage. While the use of tamoxifen as a hormonal therapy in premenopausal breast cancer is now the standard of care, no conclusive data confirm the benefit of GnRH agonists in adjuvant therapy after treatment with chemotherapy followed by tamoxifen.

As more women over the age of 35 consider pregnancy, fertility issues are becoming important areas of investigation for the adjuvant treatment of breast cancer. Whether chemotherapy-induced amenorrhea has a prognostic effect remains unclear, and further studies are warranted.

Effective chemoprevention is available for breast cancer, but it is associated with the potential for life-threatening adverse events. Accurate identification of women facing increased risk of breast cancer is therefore essential. Atypical hyperplasia is a histopathologic pattern that has been consistently associated with an elevated future risk of breast cancer.

The literature was reviewed to assess the strength of the association between atypical hyperplasia and breast cancer. The rationale for developing a nonsurgical modality to document the presence of atypia is discussed.

Ductal lavage identifies atypical hyperplasia by retrieving epithelial cells shed into the ductal system with a specially designed catheter. Women with clinical evidence of increased breast cancer risk may consider ductal lavage as a means of determining whether abnormal proliferative activity is occurring in their breasts at a given point in time from ducts yielding fluid.

Ductal lavage is a minimally invasive procedure that facilitates the detection of atypia via retrieval of breast ductal fluid that can be evaluated cytologically. It can facilitate the selection of women who may benefit from breast cancer risk reduction intervention.

Bone is the most common site of breast cancer metastases. Skeletal metastases may be associated with harmful and painful events such as fractures, spinal cord compression, and hypercalcemia. By inhibiting osteoclasts and bone resorption, bisphosphonates can interrupt the process of bone destruction and decrease the risk of skeletal complications.

A review of the literature was undertaken regarding the use of bisphosphonates in breast cancer management, with particular attention to prospective, randomized clinical trials that have influenced the treatment of bone metastases.

Large prospective, randomized trials have demonstrated that bisphosphonates are effective in reducing skeletal-related complications from metastatic breast cancer.

For many patients with osseous lesions from breast cancer, bisphosphonate therapy is a useful intervention in managing their disease. Bisphosphonates are the treatment of choice for hypercalcemia of malignancy and bisphosphonates reduce the risk of pathologic fractures, spinal cord compromise, the need for radiation or surgery to bone, and bone pain.

Tamoxifen has been the endocrine treatment of choice for patients with breast cancer. The development of selective aromatase inhibitors has offered an alternative management approach for patients in whom a hormonal approach is indicated.

The authors reviewed reports in which aromatase inhibitors were compared with tamoxifen for the treatment of metastatic disease, as well as information pertinent to their use as adjuvant therapy.

Both nonsteroidal (anastrozole and letrozole) and steroidal (exemestane) aromatase inhibitors for metastatic disease appear to provide superior efficacy and a better toxicity profile in first- and second-line treatment of metastatic disease than tamoxifen. Early results from the ATAC trial suggest anastrozole is superior to tamoxifen for disease-free survival, particularly in receptor-positive patients, and in reducing the incidence of contralateral breast cancer.

Aromatase inhibitors have important roles in optimal management of postmenopausal patients with hormone-responsive metastases in both the adjuvant and advanced-disease settings.

Overexpression of the epidermal growth factor 2 HER2 in breast cancer tissue is associated with shorter survival. Trastuzumab, a monoclonal antibody against HER2, can induce tumor responses when given alone and enhances the effectiveness of several chemotherapeutic agents.

The recent clinical data on outcomes regarding testing for HER2 overexpression and the tolerance, toxicity, and antitumor effects of trastuzumab are reviewed.

Trastuzumab use is indicated either alone or with chemotherapy only in patients with IHC 3+ or FISH+ test results and survival is prolonged in patients with metastatic disease. Cardiac toxicity differs from anthracycline cardiac toxicity and is often reversible.

The safety and efficacy profile of trastuzumab in patients with metastatic disease has led to large-scale testing of addition of the intervention in the adjuvant setting.