children. These modifications might prevent 38% of breast cancers in the United States. The benefits of moderate exercise, such as brisk walking, are seen at all age groups, including postmenopausal women. Marine omega-3 polyunsaturated fatty acids appear to reduce the risk.
Removal of both breasts before any cancer has been diagnosed or any suspicious lump or other lesion has appeared (a procedure known as prophylactic bilateral mastectomy) may be considered in people with BRCA1 and BRCA2 mutations, which are associated with a substantially heightened risk for an eventual diagnosis of breast cancer. BRCA testing is recommended in those with a high family risk after genetic counseling. It is not recommended routinely. This is because there are many different forms of changes in BRCA genes, ranging from harmless mutations to obviously dangerous frame shift mutations. The effect of most of identifiable changes in the genes is uncertain. Testing in an average-risk person is particularly likely to return one of these indeterminate, useless results.
The selective estrogen receptor modulators (such as tamoxifen) reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer. There is no overall change in the risk of death. They are thus not recommended for the prevention of breast cancer in women at average risk but may be offered for those at high risk. The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.
Statistics and Prognosis of Breast Cancer
Breast cancer is the most common cancer among American women, except for skin cancers. About 1 in 8 (12%) women in the United States will develop invasive breast cancer during their lifetime. The American Cancer Society estimates 232,670 new cases of invasive breast cancer will be diagnosed in women in the United States in 2014. About 62,570 new cases of carcinoma in situ (CIS) will be diagnosed (CIS is noninvasive and is the earliest form of breast cancer). About 40,000 women will die from breast cancer.
Breast Cancer and Novel Treatment Options
Epithelial growth factor receptor inhibitors
The epidermal growth factor receptor (EGFR/HER1) is a protein that is overexpressed among triple-negative breast cancer for which several monoclonal antibodies and small-molecule inhibitors exist. Researches have shown efficacy of cetuximab, an anti-EGFR monoclonal antibody, in combination with chemotherapy and have shown it has only modest activity.
Angiogenesis inhibitors
Angiogenesis, which is spread of a tumor via growth of new blood vessels, is considered to be an important target for cancer therapy. However, there is no data that incorporation of angiogenesis inhibitors has an impact on overall survival for women with triple-negative breast cancer. Therefore, this treatment has not yet been implied in breast cancer patients. Of agents in this class, bevacizumab has been the most widely studied. Unfortunately, incorporation of bevacizumab has virtually no impact on overall survival. This appears to be true even for patients with triple-negative breast cancer when bevacizumab was administered in the adjuvant and first-line metastatic settings.
PARP inhibitors
Inhibitors of poly (adenosine diphosphate-ribose) polymerase (PARP) are another class of agents that may be particularly useful in BRCA-mutated breast cancer, of which the majority are triple negative. The role of PARP inhibitors in the treatment of triple-negative breast cancer continues to be an active area of investigation. However, they are not commercially available for use.
PARP is involved in the molecular events leading to cell recovery from DNA damage. When PARP1, the most abundant member of the PARP family, is inhibited, double-strand DNA breaks accumulate and under normal conditions are repaired via the BRCA pathway-dependent homologous recombination mechanism. Investigators hypothesized that inhibition of PARP, in combination with DNA-damaging chemotherapeutics, would render tumors lacking BRCA function extremely sensitive. Given the shared clinicopathologic characteristics between BRCA-mutated and triple-negative breast cancers, the efficacy and safety of PARP inhibition is being tested in both settings. There are several PARP inhibitors in clinical development, such as olaparib, veliparib, and iniparib.
Src inhibitors
Gene expression profiling has suggested that triple-negative breast cancer might be preferentially sensitive to inhibition of the proto-oncogene Src. Dasatinib, a potent orally available inhibitor of Src-family kinase, is being studied in the setting of advanced triple-negative breast cancer patients.
Histone deacetylase (HDAC) inhibitors
Epigenetic mechanisms (i.e., DNA methyltransferase and histone deacetylase [HDAC] inhibitors) might play a role in the loss of ER-alpha in ER-negative breast tumors. Preclinical studies have shown that pharmacologic inhibition of these mechanisms result in re-expression of functional ER mRNA and protein. The addition of an HDAC inhibitor, vorinostat, to endocrine therapy in the setting of endocrine-resistant disease appears to restore sensitivity in select patients, a hypothesis that is being carried forward in the setting of ER-negative breast cancer.
Figure 3 Invasive ductal carcinoma of breast on mammogram
Source: Medscape.
Screening for Breast Cancer
Research has shown that routine screening between the ages of 40 and 50 is less effective. As a woman goes through menopause, the glandular tissue in her breast decreases and the proportion of fat in her breast increases. This makes the mammogram easier to interpret. Most of the mortality benefit is achieved when screening is started at the age of 50 years.
Treatment
Oncoplastic surgery
Breast-conserving surgery (lumpectomy or partial mastectomy) can often be used for early-stage breast cancers. But in some women, it can result in breasts of different sizes and/or shapes. For larger tumors, it might not even be possible, and a mastectomy might be needed instead. Some doctors address this problem by combining cancer surgery and plastic surgery techniques, known as oncoplastic surgery. This typically involves reshaping the breast at the time of the initial surgery, and may mean operating on the other breast as well to make them more symmetrical. This approach is still fairly new, and not all doctors are comfortable with it.
New chemotherapy drugs
Advanced breast cancers are often hard to treat, so researchers are always looking for newer drugs. A drug class has been developed that targets cancers caused by BRCA mutations. This class of drugs is called PARP inhibitors, and they have shown promise in clinical trials treating breast, ovarian, and prostate cancers that had spread and were resistant to other treatments. Further studies are being done to see if this drug can help patients without BRCA mutations.
Targeted therapies
Targeted therapies are a group of newer drugs that specifically take advantage of gene changes in cells that cause cancer.
Drugs that target HER2
A number of drugs that target HER2 are currently in use, including trastuzumab (Herceptin), pertuzumab (Perjeta), ado-trastuzumab emtansine (Kadcyla), and lapatinib (Tykerb).
Anti-angiogenesis drugs
For cancers to grow, blood vessels must develop to nourish the cancer cells. This process is called angiogenesis. Looking at angiogenesis in breast cancer specimens can help predict prognosis. Some studies have found that breast cancers surrounded by many new, small blood vessels are likely to be more aggressive. Bevacizumab (Avastin) is an example of an anti-angiogenesis drug.