In the 1970s, the first of several research studies suggested a bold new approach in the fight against breast cancer. Rather than opting for a radical mastectomy, the data suggested that if one adopts simpler, breast-conserving surgery followed by chemotherapy or radiation, patients do better.
As an early-career investigator just starting out in cancer biology, the findings were nothing short of riveting for me. I saw them as a potential game-changer that might possibly alter the trajectory of this dreaded disease, and to some degree my assessment was correct.
Forty years of advances have taken us from a time when disfiguring surgery was the only real treatment option to an era where we can now tailor targeted therapies for individual subgroups and even patients. While it may not be possible to get rid of someone’s cancer, innovative therapies are now enabling doctors to manage breast cancer more effectively in their patients.
But to borrow a phrase from Alvin Toffler’s, Future Shock, “that great, growling engine of change—technology” has also made the diagnosis and treatment of breast cancer a far more complicated process than it used to be. We know, for instance, that breast cancer is not one disease but at least a dozen different diseases. Let’s start with the telltale lump. You might have a ductal carcinoma, a papillary carcinoma or a carcinoma in situ, which is really a cluster of cells with calcification that feels like a lump. Within each of these categories you have tumors with widely different traits. Some grow rapidly, others remain indolent. It’s also worth noting that not all breast cancers present with a lump. In some cases, it simply shows up as a strange inflammatory rash across the breast.
I speak from personal experience. My wife of 44 years is a 13-year cancer survivor. Learning a diagnosis is a shocking thing, of course, but we were not entirely surprised when the biopsy came back positive. She has some family history of breast cancer, has very dense breast tissue and fibroid cysts. We had dealt with these conditions for a number of years. The day she discovered a tiny lump the size of a jelly bean along with discharge from the nipple we sensed that this was the one that needed to be seen. We were right. She underwent a lumpectomy, chemotherapy, radiation and hormonal therapy.
Categorizing subgroups of tumors is complicated in itself. But along with these different subgroups of cancers, oncologists have also come to realize the startling heterogeneity of individual breast tumors. Some are estrogen receptor or progesterone receptor positive, some make an excess of the protein human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. And some have all three traits. In contrast, some turn out to be negative for these hormone receptors or proteins. Depending upon the genetic traits of a particular tumor, you might want to select a different treatment course.
This became evident about six years ago, when the New England Journal of Medicine1 published the results of a clinical trial that help bring some clarity to the staging process. The study showed that a multigene assay was predictive of tamoxifen-treated, node-negative breast cancer. The assay that was used in the study analyzed the presence of 21 different oncogenes in 668 biopsied breast tumors. Here, finally, was data that showed we can actually determine the probability of two events—will a patient respond to therapy, and without therapy will they have recurrent disease?
The experimental tools used in that study have since found their way to the marketplace. While not a sure thing, they have the ability to take many of those 232,340 breast cancer cases in the US and size them up, molecularly speaking, so that clinicians can better assess which drugs may or may not work, or whether chemotherapy is even required.
One such assay, known as Oncotype DX, assesses the potential benefit of chemotherapy and the likelihood of distant breast cancer recurrence in women with node negative or node positive ER-positive, HER2-negative invasive breast cancer. The company has similar genetic tests for colon cancer and prostate cancer, and is working on one for lung cancer. Another gene expression test, called MammaPrint, looks for 70 different genes within tumor cells.
And the science doesn’t end there. We are taking patient-derived tumors at our site in North Carolina and growing them in immune-compromised mice in order to understand better what mechanisms drive these cancers. We hope to identify additional genetic markers that will lead to more improved therapies.
Most insurance companies now cover the costs of these gene expression tests. Unfortunately, for whatever reason, doctors don’t always tell their patients about them. So it is important for women (and their partners) to be their own advocate, learn about the latest tools and ask for these tests if the situation should arise.
Experts estimate that one out of eight women born in the US today will be diagnosed with breast cancer at some point in their life. While we all wish curing breast cancer were as straightforward as a course of antibiotics, the reality is that breast cancer is an incredibly complex disease. Becoming a straight A student about one’s disease isn’t just a smart thing to do, it could save your life.
New England Journal of Medicine, 351, 2817, 2004
(The post was written by Charles Harrison, an oncologist research who worked at Charles River until 2014.)