Guest Blog Post: Important Advice if You’re Considering Mastectomy

Ingrid Meszoely, M.D. is Associate Professor of Surgical Oncology and Clinical Director, Vanderbilt Breast Center at Vanderbilt-Ingram Cancer Center.

Following the completion of several large studies in the late 1980s and early 1990s involving thousands of women, it was clearly determined that the number of years a woman lived following breast cancer surgery was exactly the same whether she underwent mastectomy (removing the whole breast) or lumpectomy (just removing the part  of the breast with the cancer). This was a big breakthrough for breast cancer treatment with the realization that more surgery doesn’t result in better outcomes.  Initially this resulted in a trend of women choosing lumpectomy over mastectomy in order to preserve their breasts.

However in recent years, as Dr. Kummerow and many other researchers have found, there is a nationwide trend in choosing mastectomy over lumpectomy despite there being no clear survival advantage.  In addition, many women choose to undergo mastectomy of the non -affected breast despite the fact that the risk of developing cancer in this breast is very low and that it does not have any effect on survival from their current breast cancer.

As a breast cancer surgeon, I see this same phenomenon in my own practice.  The choice of mastectomy on one or both sides is often driven by multiple factors including the fear of cancer coming back or a new cancer on the other side and the wish to do everything one can to prevent this.  This often provides some sense of control and peace of mind in the setting of an overwhelming diagnosis.

When a woman is diagnosed with early breast cancer and given the choice of mastectomy or lumpectomy because she is a candidate for either procedure, the options should be considered carefully.

It should be clearly recognized that mastectomy does not provide 100 percent protection from cancers coming back. Cancers often come back at other sites outside of the breast before they return in the area of the removed breast tissue.  Because mammograms or other imaging studies are not routinely used after mastectomy, the finding of recurrences along the chest depends on continued routine self -exam and clinical exam by their doctor when the tumor is large enough to feel as opposed to being detected on mammogram when it is very small.

Mastectomy is also associated with increased complications compared to lumpectomy and these are often related to the reconstruction, which can be discouraging.  It is even more devastating when there are complications related to the unaffected breast when women choose mastectomies on both sides.

Lymph node surgery often is performed in the setting of mastectomy.  If just a single lymph node is found to be involved with breast cancer, removal of additional lymph nodes is recommended which can result in added complications. However if a lumpectomy is chosen, generally 3 or more lymph nodes need to be involved with cancer before more lymph nodes are removed.

When a woman presents with newly diagnosed early breast cancer and is put in the position of making a decision between lumpectomy and mastectomy, a thoughtful discussion should be initiated with her treating physicians.  Ultimately, the decision is very personal and she should choose the procedure that suits her lifestyle and provides her with the greatest sense of wellbeing.

 

PALB2 Gene Mutation Affects Breast Cancer Risk

Having a family history of breast cancer nearly doubles a woman’s risk of developing the disease and genetic factors are known to play a major role in the origin of breast cancer.

The BRCA1 and BRCA2 genes were identified as major breast cancer susceptibility genes nearly 30 years ago and it is estimated that these gene mutations explain about 50 percent of familial breast cancer cases.  BRCA1 and BRCA2 mutation tests have been widely used in high risk women (e.g., women with a strong family history of breast cancer) for risk assessment and management which may include prophylactic surgical and drug therapy intervention.

However, a significant fraction of familial breast cancer cases remain unexplained. A recent study identified the PALB2 gene as another major breast cancer predisposition gene. The PALB2 (Partner and localizer of BRCA2) gene produces a protein that is crucial for key BRCA2 functions. Mutation carriers of this gene were found to have a 35 percent risk of developing breast cancer by the age of 70, triple the risk seen in the general population.  For breast cancer diagnosed before age 40, having PALB2 mutations was related to an 8 to 9-fold increased risk.  It is estimated the PALB2 mutations explain about 2 to 3 percent of familial breast cancer risk. This study expanded our knowledge of genetic contributions to the familial profile of breast cancer.

Currently, the benefit and risk of deploying preemptive measures like surgery or drug therapy based on PALB2 mutation status is unknown. While the utility of applying PALB2 mutation information for risk management of high risk populations needs to be further investigated, individuals with known mutations of this gene are encouraged to seek genetic counseling because PALB2 mutations are also known to increase the risk of pancreatic cancer and may increase the risk of ovarian cancers. Mutations in PALB2 are very rare in the general population. Thus, screening for PALB2 in the general population appears to be unnecessary.

Xiao Ou Shu, M.D., Ph.D., MPH
Ingram Professor of Cancer Research
Vanderbilt-Ingram Cancer Center

Guest Blog Post – The Biologic Picture of Melanoma

Jeffrey A. Sosman, M.D., Director, Melanoma and Tumor Immunotherapy Program
Vanderbilt-Ingram Cancer Center

In the past 10 years, mutations found in melanoma (the most deadly form of skin cancer) have led directly to the development of effective therapies. One example is the BRAF mutation and its inhibitor drug vemurafenib.

The New York Times reported on a new finding uncovered in the DNA of a large number of melanomas tested with extensive DNA sequencing of the whole genome.  This new mutation found by two independent groups is actually not present in a gene that produces a functional protein or enzyme.  Instead, it is a mutation in the portion of the DNA that regulates the expression of an enzyme, telomerase. Telomerase protects the chromosomes from breakdown and the cell from death. High levels of telomerase are seen in many cancer cells, including melanoma, and it protects the cancer cells from a normal dying process.

In a mechanism previously never reported, the newly discovered mutation changes the regulatory portion of DNA so it may be very vulnerable towards activation. In this way, the mutation indirectly allows the telomerase level to increase.

This mutation is found in these exact locations in about 70 percent of melanomas. The mutation provides a link between the BRAF mutations and the regulatory portion of another gene.

The new discovery adds one more piece to the biologic puzzle of melanoma. With each additional piece we are closer to completing the biologic picture of melanoma, which will further our ability to define treatment approaches to kill this deadly cancer.