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.
Other targeted drugs
Everolimus (Afinitor) is a targeted therapy drug that seems to help hormone therapy drugs work better. It is approved to be given with exemestane (Aromasin) to treat advanced hormone receptor-positive breast cancer in postmenopausal women. It has also been studied with other hormone therapy drugs and for treatment of earlier-stage breast cancer. In one study, letrozole plus everolimus worked better than letrozole alone in shrinking breast tumors before surgery. It also seemed to help in treating advanced hormone receptor-positive breast cancer when added to tamoxifen. Everolimus is also being studied in combination with chemotherapy and the targeted drug trastuzumab.
Zarish Umar
Independent Scholar
See Also: Breast: Major Pathologies; Cancer Stem Cells: Overview; Fetal Stem Cells.
Further Readings
American Cancer Society. Cancer Facts and Figures. American Cancer Society. http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014 (Accessed November 2014).
Foukakis, T., et al. “Prognostic and Predictive Factors in Early, Non-Metastatic Breast
