Katherine Crew, MD, is a physician-scientist whose work in breast cancer risk, prevention, and screening has helped move the needle in breast cancer research. Dr. Crew is a member of the Cancer Population Science research program at the Herbert Irving Comprehensive Cancer Center, associate professor of medicine and of epidemiology at Columbia University Irving Medical Center, and a medical oncologist at NewYork-Presbyterian Hospital.

Weve made a lot of strides in the past few decades and part of that is because we are detecting breast cancer a lot earlier with improved screening and due to our improvements in treating breast cancer, says Dr. Crew. There are always more improvements to make along the way but overall survival for breast cancer, since the 1980s, has improved by about 40%, and its due to all of those efforts, including increased advocacy and increased awareness of this disease.

Where are we now in treating breast cancer?Through epidemiological studies, we have a better understanding of the main risk factors for breast cancer, whether it be age and reproductive factors that influence exposure to the hormone, estrogen, and were learning a lot more about genetic risk for breast cancer.

Back in the mid-1990s it was all about BRCA1 and BRCA2 mutations but now, in the past several years, were testing for multiple genes that can predispose to breast cancer as well as other cancers. And with next generation sequencing, were able to sequence the whole genome much more cheaply and much more quickly. This has led to an increase in our understanding about genetic susceptibility to breast cancer in particular.

Once a person knows about her genetic risk factors or that they are predisposed to breast cancer, what then?We know if a woman has a genetic predisposition, she has the option for enhanced screening, with not just mammography, but more sensitive screening tests like breast MRI. If she has a high penetrance gene she may opt for prophylactic mastectomy. Certainly when Angelina Jolie wrote her Op-Ed in The New York Times about getting a bilateral mastectomy after she found out she had a BRCA1 mutation that really helped to increase awareness.

Now that were finding these more moderate risk genes it has becoming harder to know where to draw the line. We dont want women to do unnecessary surgery or to do unnecessary procedures because that may be potentially harmful. I think were still learning what to do with that information. Knowing more about a persons genetic risk has definitely helped to make breast cancer risk much more personalized and we are always trying to provide the right intervention for the right level of risk, per individual.

There are many types of breast cancer. Can you give us the lay of the land of the main subtypes?The different subtypes of breast cancer all behave differently and we treat them differently. The most common is the estrogen receptor positive breast cancer, which counts for about 70% of all breast cancers and we know that these types of breast cancers respond very well to anti-estrogen therapy. More recently weve been using a class of drugs called aromatase inhibitors in post-menopausal women. In many ways thats been one of the most effective targeted treatments that weve had for breast cancer we can see up to a 50% to 65% relative risk reduction in breast cancer relapse with these drugs.

There is HER2-positive breast cancer and recently, theres been an explosion of new drugs for treating this subtype. Within just the past few years, at least four or five additional drugs have been approved for HER2-positive breast cancer. Although it is a more aggressive form of breast cancer, it is also a type of breast cancer that responds well and is very sensitive in general to chemotherapy and targeted therapy. Even in patients who have metastatic disease, women are living longersometimes for more than five yearswith advanced breast cancer.

The most challenging type of breast cancer to treat is triple negative breast cancer, meaning that it is negative for the two hormone receptors estrogen and progesteroneand also negative for the HER2 receptor. We cant treat it with anti-estrogen therapy and we cant treat it with any HER2 targeted therapies. In this case the main treatment option is chemotherapy, which has its own set of side effects associated with it.

Is this a focused area of research right now?Yes, its an area very ripe for new discovery and research. Recently there was drug approval for immunotherapy for triple negative breast cancer, particularly in combination with chemotherapy. Immunotherapy is a very new type of therapy thats gotten a lot of attention in the press and in the oncology world.

Tell us how immunotherapy could impact breast cancer.Currently, immunotherapy is approved in patients with metastatic triple negative breast cancer but there are a lot of clinical trials that are looking to expand the use of this medication for other breast cancer subtypes. Typically in cancer in general we test these new drugs in patients with advanced cancer who have fewer treatment options and in those cases we may only prolong their survival by a few months. Its much more exciting when we can then take these drugs, if theyre found to be safe in patients with early stage disease, to see if we can improve cure rates. There are ongoing trials testing immunotherapy in patients with early-stage breast cancer, especially if they have high risk disease, to see if we can prevent a relapse and therefore cure them.

What are the other exciting areas of breast cancer research right now?A big trend within oncology and within breast cancer in particular is the de-escalation of therapy. Can we spare some patients from unnecessary treatment? We dont want to over treat breast cancer. We want to treat the high-risk patients but the ones with a more favorable breast cancer, we want to spare them some of the side effects of chemotherapy, for example.

One major breakthrough is as we understand the biology of these tumors a little bit better, we can better classify patients. There are different molecular tumor tests we can use now, including Oncotype Dx, MammaPrint, breast cancer index all of these new tumor tests gives us the opportunity to personalize a womans breast cancer care. Based upon a womans tumor biology, we can assess who needs chemotherapy, who may benefit from extended hormonal therapy, who can do well with just five years of anti-estrogen therapy, and then we can spare them from a lot of the side effects that weve seen from some of these drugs. I think that de-escalation of care has helped cut costs and certainly reduces long-term side effects in our breast cancer patients. We dont want to keep adding on expensive treatments on patients who dont necessarily need it.

You run the High-Risk Prevention Clinic. Whats new in prevention?Similar to the breast cancer treatment field, in the preventive setting you have to look at this not as a one-size-fits-all for women. We can now better refine what a womans risk is and give individualized guidelines for them. Prevention is getting more complex. We dont just test for BRCA1 and BRCA2 genes; there are multi-gene panels that we can test for. Now theres a lot of interest in polygenic risk scores (PGS), so rather than looking at one gene we can look at a bunch of genetic variants sometimes hundreds of genetic variations and come up with a risk score based upon those hundreds of variants. Based upon that score, we place women on a spectrum of risk and then use that to make recommendations about screening, lifestyle modifications, preventive surgeries, and even medications. For example, anti-estrogen drugs have also been shown to be effective in the prevention setting.

How has screening for breast cancer evolved or changed?There are major advances on the screening front as well. For a long time we mainly only had 2D digital mammography and now we have 3D mammography, or tomosynthesis. Rather than just having two views of the breast you can have serial slices of the breast and that can help to increase the sensitivity of the mammogram, particularly in women who have dense breast tissue because having dense tissue can lower the sensitivity of the mammogram for early detection.

There is actually a lot of controversy around screening. Just as we know there are more than one type of breast cancer and more than one level of risk, were trying to adopt less of this sort of one-size-fits-all for breast cancer screening. For instance, not all women need to get yearly mammograms, maybe just higher risk women with dense breast tissue could get enhanced screening with either ultrasound or MRI. But for the majority of women who are not high risk, perhaps we can think about cutting back on mammography screenings. Current guidelines are that if you are average risk you can wait until youre 50 to get mammograms every two years, rather than yearly. Maybe less frequent screenings can also reduce some of the harms of screenings, like increased biopsies.

What does the future hold for breast cancer research and treatment?All of the new drugs and targeted therapies have definitely incrementally advanced the field.

The most exciting is this idea of precision medicine, both for prevention and for treatment, and using genetic information to assess breast cancer risk, having the genetic information of the tumor tissue to assess the aggressiveness of the cancer and being able to tailor treatments specific for individual patients is what we are working towards. I think that more than anything else having that genetic information tailoring our carehas really put more tools in our tool box in terms of what we can offer patients.

-Interview by Melanie A. Farmer

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Q+A: Katherine Crew, MD, on the Many Advances in Breast Cancer and What's to Come - Columbia University Irving Medical Center

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