Eric Winer, MD, director of Breast Oncology at Dana-Farber’s Susan F. Smith Center for Women’s Cancers, gave the William L. McGuire Memorial Lecture at the San Antonio Breast Cancer Symposium in December 2016. This annual lecture and award are given to a breast oncologist who made significant contributions to the field. The lecture is abbreviated below.
When I was a first-year oncologist in 1990, there were 150,000 cases of breast cancer each year in the U.S. and 44,000 deaths. Breast cancer back then was viewed as a single disease. When patients asked me, “What kind of breast cancer do I have?” I would say, “You have stage II breast cancer,” but I didn’t have the understanding or the words to talk about subtypes.
Most breast cancers in 1990 presented as a lump or mass. Extensive surgery was often performed, causing psychological and physical distress. Chemotherapy and hormonal therapy were relatively recent additions at the time. For women with metastatic breast cancer, the treatment options were very limited. This was the era of autologous bone marrow transplantation with high-dose chemotherapy, which led to severe toxicity and proved to be no better than standard therapy.
Breast cancer advocacy, which has been so important over the past quarter of a century, was in its infancy.
In the last 25 years, surgeons have led the way in offering less invasive approaches. There’s been a reduction in radiation toxicity and the option for fewer treatments at higher doses. There have been advances in chemotherapy and immunotherapy, and the widespread use of anti-HER2 therapy. Treatment is more individualized, based on disease characteristics, stage, and patient preference. For metastatic patients, we have an array of new chemotherapy and hormonal approaches.
The most notable advance is recognizing the importance of tumor heterogeneity, and the identification of different subtypes of breast cancer. So, we now think of breast cancer as a family of diseases: HER2-positive, triple-negative, and ER-positive. The ER-positive type is further divided into tumors that are low-grade, or luminal A, and higher grade, or luminal B.
We’re also paying more attention to differences in patients, such as obesity, inflammation, immune profile, and others.
But we’re still left with sobering statistics. In 2016, it was estimated that there would be more than 246,000 cases of invasive breast cancer in the U.S., 61,000 new cases of DCIS, and 40,000 deaths. Worldwide, of course, it’s even more dramatic, with 1.7 million new cases per year and over half a million deaths. Suffering continues for women with breast cancer, in spite of the improvements that we have made.
As we look ahead there are three areas that need focus: resistance to treatment, overtreatment, and health equity.
Breast tumors can become resistant to chemotherapy and other treatments, and in the developed world, treatment resistance is probably the major cause of breast cancer death, particularly for patients with triple-negative or luminal B breast cancer, and a subset of patients with HER2-positive disease.
On the other end, overtreatment is a problem for women with DCIS, or stage I or II disease. It is not a concern for most patients with triple negative or luminal B disease, but for the others, we need to identify who can do well with less.
There are many unanswered questions. Which patients with ER+ breast cancer truly need chemotherapy? Do patients with favorable gene signatures who have an excellent outcome after five years of endocrine therapy need prolonged medication? Are there patients who could do well with even less therapy? Although we think of endocrine therapy as being easier than chemotherapy, for many patients, taking a pill with side effects for an additional five or more years is simply more than they can accept, particularly if the benefits are minimal or none.
In HER2-positive disease, our group at Dana-Farber led a single-arm trial in patients with node-negative HER2-positive breast cancer, largely stage I. With a median follow-up of 73 months in this group of more than 400 patients, the 5-year survival is 96.3 percent, and there were only three distant recurrences. This is with a very simple chemotherapy regimen not totally devoid of toxicity, but far easier than others.
When it comes to health equities, we can’t begin to imagine how many unnecessary deaths from breast cancer occur as a result of inadequate health care or lack of access. Race, poverty, limited education, and lack of health insurance are among the many causes of disparities in the U.S. Age also plays a role in breast cancer survival, with women under 30 and over 80 having the worst outcomes.
In the next decade, we have the potential to eliminate half of all deaths from resistance by continuing our basic and clinical research. Now that we have identified the problem of overtreatment, we can begin to tackle it. At the same time, we can begin to back off on therapy for those who will do well with less. Health equity will be our toughest challenge, and progress in this complex arena is imperative.