Breast Cancer Awareness Month Spotlights Progress With Personalized Medicine

Sheldon M. Feldman, MD

As personalized medicine takes center stage in the breast cancer treatment paradigm, therapies targeting specific cancer-driving mutations or gene amplifications, such as HER2 overexpression, have transformed outcomes, particularly for those with advanced disease, according to Sheldon M. Feldman, MD.

“The overarching issue in treating [patients with breast] cancer is that tthe most effective approach is identifying specific targets that drive the cancer,” Feldman explained in an interview with OncLive^® during Breast Cancer Awareness Month. “If you can identify the target that's making the cancer grow, and you can hit that target, then the cancer is stopped, and the patients are cured. It's all about finding more and more targets to treat. The science is advancing so quickly as more targets are being identified, so that's where a huge amount of the progress in preventing death from breast cancer has come along.”

In the interview, Feldman discussed the importance of tailored treatment approaches in breast cancer care, emphasized the need for early disease detection, and highlighted the significance of the new categorization of HER2-low breast cancer for expanding access to effective new agents for patients with this disease subtype.

Feldman serves as chief of the Division of Breast Surgery and Breast Surgical Oncology, the director of Breast Cancer Services, and a professor in the Department of Surgery at Montefiore Einstein, in Bronx, New York.

OncLive: What is the importance of Breast Cancer Awareness Month, and how does it encourage timely cancer screenings?

Feldman: Breast cancer is such an important part of our world. It's hard to talk to anybody, [whether it be a] friend, family member, or colleague, who has not in some way been affected by it; it's embedded in our social fabric. The good news is that we're doing better at treating patients with breast cancer with more minimally invasive approaches and better outcomes, but that is contingent on the [diagnosis]. The earlier a diagnosis is, the better.

It is a scary thing, for both women and men to think about the possibility of having a test that could lead to a diagnosis of cancer. What I often say to patients who are diagnosed with breast cancer when it's found early through screening is that they're basically asymptomatic; they just went for a test, or maybe feel a lump in their breast. They are not sick with breast cancer, they've been diagnosed with breast cancer—which is an important difference—and any treatment that we might recommend for them is directed at them staying healthy rather than treating them. It sounds a bit obvious, but it's very impactful for patients when they hear that.

Once [a patient] is diagnosed with cancer and hear that word, [they] think, ‘Oh my God, this is it,’ [raising] the idea of awareness. Being a woman and getting older puts patients at an increased risk for developing breast cancer. That's the reality of it. For women to understand, the guidelines for screening, which allow us to make a very early diagnosis with screening mammography. [it is] also [crucial] to be aware of any breast symptoms they have. If they feel a lump, they're having unusual pain, hey have discharge from their nipple, or they have a rash on their breast, [they should be able] to let someone know that there may be a problem. That then needs to be looked at and evaluated.

October has been Breast Cancer Awareness Month for a long time now, and now every month is a different disease of the month to highlight the awareness and serve as a reminder. Breast cancer is such an important disease, but so easy to diagnose early and very curable for the majority of patients.

How has the use of personalized medicine evolved in breast cancer management?

It is important for patients to understand that, although we use the [singular of] breast cancer, breast cancer is not one disease. There are different stages of cancer [spanning from] early to more advanced, but there are also different subtypes of breast cancer, which have different prognoses and treatments recommended. There are 2 sides to the equation: we have the biology and the stage of the cancer, and then we have the medical specifics of the patient. This [includes] if they're young vs old, if they have children, and whether they have other health problems. This gets considered when an individual treatment plan is decided upon.

For example, a younger woman diagnosed with an early-stage breast cancer, if she's going to have breast conservation, [may] also receive adjuvant radiation to the breast to reduce the chance of the cancer coming back. However, we now know if that same cancer is diagnosed in a woman who's a bit older than 65 or 70 years, she may not need to [undergo] radiation. This is because studies have shown that in this age group, the benefits of radiation are not [observed], and no radiation is certainly a safe option. That may not be the case for younger patients.

We get even more into the weeds when looking at patients who have different types of breast cancer. We look at tumor markers or receptors, which [show whether] a tumor is responsive to hormones in a woman's body, and that hormone-blocking medicine is a very effective treatment. There is a target there to treat, which is the estrogen receptor. Approximately 25% of women have a particular subtype called HER2 overexpressed [breast cancer]; that is an oncogene or collection of genes in the cancer itself. We that used to think that would be bad news for patients [to have this subtype], because those patients all did worse. However, approximately 15 years ago, scientists came up with an antibody that specifically hits those genes. [Patients are] now receiving these monoclonal antibodies, and they’re very effective.

What's the significance of the new classification of HER2-low breast cancer, and how does this assist with tailoring treatment approaches?

[The HER2-ultralow subtype] is being used mainly for patients who have more advanced, stage IV disease; these are patients who initially [progressed on] other treatments. It used to be that the HER2 oncogene was either positive or overexpressed, or amplified or not overexpressed. This [new] category of HER2-low [comprises] patients who still experience benefit with anti-HER2 therapy.

Fam-trastuzumab deruxtecan-nxki [Enhertu; T-DXd] is a blockbuster for those patients, so this is a major advance, particularly for patients with advanced disease who [progressed on] other therapies, [were considered HER2-negative] in the past and are now being designated HER2-low. It opens the door to this treatment, which has been shown to be very effective and not even considered in the past for this subgroup of patients. It's a big advance and very important.