Need for Genetic Testing Becomes More Pronounced in Breast, Gynecologic Cancers as Targeted Approaches Abound

Lan G. Coffman, MD, PhD

The need for genetic testing in breast and gynecologic cancers has become more prominent in recent years, according to Lan G. Coffman, MD, PhD, who added that the information yielded from these tests is needed to determine whether a targeted approach will be beneficial.

“As we expand our knowledge on the predisposition of breast and gynecologic cancers, we're learning more about how one's genes influence risk, as well as our ability to treat these cancers,” Coffman explained. “BRCA mutations, for example, are one of the most commonly acknowledged genetic syndromes. BRCA1/2 mutations are genetic predispositions related to DNA damage, which significantly increases a patient’s risk of developing breast or ovarian cancer.”

In an interview with OncLive^® during the 2020 Institutional Perspectives in Cancer webinar on Precision Medicine, Coffman, an assistant professor at the University of Pittsburgh Medical (UPMC) Center Hillman Cancer Center, discussed the role of genetic testing in breast and gynecologic cancers and the many advances made with targeted therapies. 

OncLive: Could you expand on the critical importance of genetic testing in patients with breast and gynecological cancers? 

Coffman: All [patients with] ovarian cancer are recommended to undergo germline testing for BRCA mutations, both to understand potential treatments for themselves, as well as what their family members may be at risk for. Knowing this information allows us to institute appropriate screening. Certainly, guidelines for breast cancer are different in terms of the number of family members affected, age, and the type of breast cancer; however, it’s something we should consider for all women who have breast or ovarian cancers.

Germline testing certainly influences what we do for family members, but it also guides treatment decisions for the patients themselves. PARP inhibitors capitalize on these mutations in DNA damage repair. If a woman harbors a BRCA mutation, they're more likely to respond to PARP inhibitors. [That information] provides us with a better idea of how they should be treated. 

We're also doing more somatic testing. We are trying to understand what genes are mutated in the tumor themselves that were not inherited from family. We find that, especially in ovarian cancer, a large number of women do not have germline BRCA mutations, but they have somatic mutations—both in BRCA and in other genes related to DNA damage repair. That information also influences how patients might respond to targeted therapies, such as PARP inhibitors.

What are some of the advances made with targeted therapy across breast cancer subtypes?

We are the furthest along with targeted therapies in the breast cancer space. For a long time, we understood that breast cancer is not just 1 cancer type; it’s actually many different diseases that we lump together. Breast cancer that is ER-positive versus breast cancer that overexpresses HER2 versus triple-negative breast cancer (TNBC) all behave very differently, and as such, we treat them differently. If we look at ER-positive breast cancer, targeted therapies have been the standard of care for a very long time; these therapies have definitely changed the treatment landscape. Largely, that targeted therapy is endocrine therapy; here, we are capitalizing on the dependence of those cells to use estrogen to help them grow and survive. We've also used antiestrogen strategies to treat these cancers. 

More recently, we've added other drugs that block synergistic pathways, such as cell cycle inhibitors or CDK4/6 inhibitors, which are now the standard of care for use in combination with endocrine therapy in patients with metastatic ER-positive breast cancer. Ultimately, we know a lot about targeted therapies in this space and use them to great effect. Similarly, we have HER2-targeted agents for patients with HER2-positive breast cancer, such as antibody-drug conjugates, which have changed the way that we treat these patients. These agents have significantly improved outcomes.

Has progress with targeted approaches lagged behind in TNBC?

We have the fewest targeted agents for patients with TNBC. In fact, until recently, we’ve been relying largely on chemotherapy. [However,] we know that TNBC is more enriched for BRCA mutations; thus, the use of PARP inhibitors capitalizes on this inability to repair DNA damage and has allowed us to use targeted therapies for this disease. Moreover, we now have a new approval for an antibody-drug conjugate that targets TROP2, which is a protein that is expressed in many TNBC cells. We’re starting to make progress here, as well.