Genomic Profiling Offers a Personalized Approach to Breast Cancer Treatment

M. Michele Blackwood, MD, FACS

Genomic profiling is a personalized approach that essentially analyzes a tumor's genetic makeup to reveal the specific mutations that drive its growth. With a contrasting approach to that of traditional “one-size-fits-all" therapies and by allowing for better understanding of the cancer's unique makeup, experts can use genomic profiling to tailor treatment plans to maximize effectiveness and minimize adverse effects in the breast cancer space.

“We are very lucky that this field has so many options for patients, and we love being able to tailor it to the patient, tailor it to her breast cancer, and tailor it to her health,” M. Michele Blackwood, MD, FACS, told Targeted Oncology^TM in an interview.

In the interview, Blackwood, director of breast surgery, RWJBarnabas Health, director of women’s oncologic health, RWJBarnabas Health and Rutgers Cancer Institute, and head of breast surgery, Cooperman Barnabas Medical Center, provided an overview of the significant advancements with personalized medicine with genomic testing in the breast cancer space.

Targeted Oncology: Could you walk us through the current landscape of breast cancer treatment and how personalized medicine is changing the field?

Blackwood: Breast cancer treatment has changed dramatically in the past 10 to 15 years, but a lot of changes are occurring quickly right now. The changes occur in 4 different areas: 1 is breast surgery, 2 is systemic treatment, meaning chemotherapies or antiestrogen treatments, 3 is breast imaging and breast screening, and 4 is radiation oncology. Everything is essentially personalized to the patient, to their physical status, and to the cancer itself.

Breast surgery has come a long way as far as restoring [patients] to the way they look and feel about themselves. Breast cancer surgery comes in multiple options, [including] mastectomy and lumpectomy. In those realms, however, there are a lot of different options. Many times, we can do a lumpectomy, and we do a breast lift on both breasts at the same time or reshape the breast or a reduction, and many [patients] feel comfortable and are happy with this choice. The second option is for mastectomy. As it used to be, we took off all the breast tissue, a lot of the skin, sometimes the muscles, a lot of lymph nodes. That essentially is not what we do anymore. Many times, we are able to do what looks like nipple-sparing mastectomy where the breast looks and feels like the breast when it is done. We restore sensation with a nerve graft, we take the breast tissue out, and we essentially leave the entire skin and/or nipple so that a [patient] looks and feels like herself when she wakes up. Those are big picture items. They have to do with the patient, the type of cancer they have, and what they look like for their overall health.

3D rendered medically accurate illustration of breast cancer: © SciePro - stock.adobe.com

There are also a number of [patients], if they do a mastectomy, that are choosing to go flat, which means no reconstruction. This is something we used to do in the 1980s and 1990s. We morphed into offering reconstruction at the same time as we did a mastectomy. The pendulum is swinging a little bit the other way, and some [patients] choose it because of their overall health or just for personal preference. Some do not want other operations that have to be essentially cosmetic later on to kind of shape the breast tissue. There are a lot of options for patients out there, which is nice because then patients can choose what they feel comfortable with. The problem with that is there are a lot of options out there, so it is a double-edged sword because sometimes patients come in and do not know how to make a decision.

Can you discuss options like chemotherapy and systemic treatments?

Everybody who has invasive cancer gets some form of treatment either before or after surgery. Chemotherapies are very targeted now to the type of cancer that the patient has. We give chemotherapy prior to surgery to either shrink the tumor down or to eliminate the tumor in the breast prior to surgery. I tell patients who have stage III or IV cancer that it is kind of like you would not renovate a house that is on fire. First, you put out the fire, then you renovate afterwards. That does give a lot more options to patients, and they can do their surgery after their systemic treatment. We get rid of the cancer cells in the breast, and we get rid of the cancer cells in the body.

The other thing is that after a [patient] has her surgery, she is going to, if she has not received chemotherapy, get something afterwards. There are 4 basic types of breast cancer, estrogen receptor-positive breast cancer, estrogen receptor-positive and progesterone receptor-positive breast cancer, HER2-amplified breast cancer, which is about 18% of breast cancers, and then triple-negative [breast cancer]. These 4 different breast cancers are treated very differently. Some are treated with pills, some are treated with injections, some are treated with a yearlong treatment, some are treated with 3 to 4 months of treatment, some are treated with 5 to 10 years [of treatment]. It is a lot to go over here. But when a patient meets with their breast cancer surgeon, the breast cancer surgeon acts as the quarterback and educates them on the different options that are available to them and then guides them to probably what we think is the best treatment.

What can you discuss about breast imaging and screening?

We have had some interesting dialogues about screening and imaging because we now understand a lot more about patients’ risk of breast cancer. If a [patient] is at a high risk of breast cancer, that means she might get screened as early as 20 or 25 years old, depending on her gene mutations, her family history, and other biopsies. We are seeing breast cancers earlier than we used to see them. The rates of breast cancer in the under-40 crowd is increasing and has been for 10 years. Olivia Munn is in her early 40s and is an actress. She just had breast cancer in both breasts. But part of it was that she got an MRI screening due to her family history. She went ahead and had an MRI.

MRIs are different from mammograms and are actually performed with a contrastthat is given intravenously at the time of the MRI. Most breast MRIs are done with both breasts being done at the same time. The [patient] lies face down in the MRI machine, and then many times the head and shoulders can be somewhat out. Even some of my patients who are claustrophobic can do this. The other thing is there is no compression of the breast. The [patients] who dread that mammogram, compressing your breast, some of them say to me, I just want to do MRIs in the future. Unfortunately, that is not an option because mammograms can pick up precancers that we might not see on MRI. MRIs are a good tool for high-risk patients, for patients who have had breast cancer in the past, and for patients who have a family history or a gene mutation that causes breast cancer. Those patients need to be guided by a breast surgical group that has a high-risk clinic. We have patients come to see us who don't have breast cancer. Every year we get their imaging, and we do their breast exams. We also talk about prevention. It is a triad of care that does help [patients] either prevent breast cancer or treat breast cancer at a very early stage, which is of course, one of the things we want to do.

Can you discuss the changes in radiation oncology?

Radiation is hard to describe to patients. I try to describe it as a beam of light across their breast, and it comes in a lot of different varieties. It used to be that it was 6 weeks' worth of treatment for 1 breast, and the patients laid down on the table and had to have it Monday through Friday for 6 weeks. I was just discussing this with my aunt this weekend who, 20 years ago, had breast cancer and talked about her radiation therapy after her lumpectomy. I said to her, well a lot of times we do not do that now in postmenopausal [patients]. We can do 3 weeks’ worth of treatment, we can do 5 days for some [patients], sometimes we can forgo radiation.

Radiation is not chemotherapy. It is not your hair falling out; it is not an IV. It is well tolerated, even by some of my [older] patients. What it does is it reduces the risk of recurrence. That obviously helps with treatment and cure. It is not one-size-fits-all anymore for radiation therapy as well. We are very lucky that this field has so many options for patients, and we love being able to tailor it to the patient, tailor it to her breast cancer, and tailor it to her health.

How does genomic profiling fit into the overall strategy for personalizing breast cancer care?

Genomic profiling of breast cancers is poorly understood. Genomic profiling means that we look at the cancer itself, sometimes right after the biopsy, we take the tumor, and we do a deep dive into the actual genes that cause that cancer to grow and proliferate, and to give it its signature, if you will.

Genomic profiling took off about 20 years ago, especially for estrogen receptor-positive breast cancers. What we found is that many [patients] may not need chemotherapy. It is not about particularly just the size of the tumor and the stage of the tumor and the cancer, but it is about how the tumor behaves. If we do the genomic profiling of the tumor, and there are different ones out there, patients like the idea that it predicts and it can be prognostic and tell us how that tumor will behave and whether the patient would benefit from chemotherapy vs just benefiting from having an anticancer or antiestrogen pill. It has changed the way we drill down towards the patient and their tumor.

The genomic profiling is increasing. However, it is not just about hormone-positive breast cancers anymore. We are looking at the genomic profiling of many more tumors, whether they are triplenegative or caused by other genes. There are companies now that we can send these tumors to that can look closely at these cancers and tell us this cancer is more aggressive than we thought, or it is being driven by this gene mutation, so take this treatment and not that treatment.

We also do genetic profiling of the patients. The American Society of Breast Surgeons, a number of years ago, came out with the recommendation that anyone with breast cancer should consider getting gene testing done. Gene testing is done either on the patient's saliva or their blood. It looks at whether they have a gene that causes breast cancer. There are some that can cause uterine cancer, ovarian cancer, gastrointestinal cancer, or colon cancers, so it is important for the patient to be tested for this and to consider it for her extended family. It also can be helpful for patients, particularly if they are young, because they want to know what other cancers we can prevent by making sure that, if they have a gene mutation, we can be able to look out and screen for those other cancers earlier than we would normally.

Are there any specific subtypes of breast cancer where genomic profiling is particularly valuable in guiding treatment decisions?

Yes and no. I do think this is the future of cancer care in general. Genomic profiling of tumors has evolved. There are some companies now that follow patients for recurrences in their bloodstream. Some of this is very experimental, and basically, when the patient is multiple years out from their cancer treatment, we take a blood sample, and check for, essentially, DNA in their bloodstream to see if they have any cancer cells floating in there. I do believe this is going to be the future.

The problem with genomic profiling tumors is it kind of got ahead of the treatments. What I mean by that is we found gene mutations, and we can pinpoint a lot of gene mutations, but we may not have the actual drug or treatment that goes with it. The other part is we have also seen gene mutations that occur in the tumor, and the medicines that should fight against it did not work. The question is, why is that? The reality is that many cancers are not just driven by 1 gene or 2 genes, but sometimes by multiple genes. There is probably some sort of interaction between these genes. This is an exciting future for cancer treatment and breast cancer treatment particularly. I think there's a lot more to come on that.

I think one of the things that people should know is that not all of this is ready for primetime treatment, but it is getting there. One also might have heard of drugs like [pembrolizumab (Keytruda)] that have been used for multiple different cancers. We had looked at breast cancers to see if they expressed PD-L1. At the beginning, we found that if you express PD-L1, pembrolizumab could fight against these cancers. Well, in reality, there are probably breast cancers that can be now found that can be helped cured by the same drugs, even if the cancer doesn't express PD-L1. There are many theories about it, and there is some exciting work being done. But sometimes, the testing gets ahead of the treatments, and sometimes, the treatments get ahead of the testing. These are the realities of cancer treatment. Many treatments that we give after we do the surgery are considered “preventive chemotherapy” or “preventive estrogen receptor pills.” We know that if we do not give it, some people will recur.

We do tend to give [patients] antiestrogen pills at least for 5 years, sometimes as long as 10 years. The reason for that is that it is like having strep throat. One can have an abscess in the back of your throat, the doctor may open it, and the pus comes out, but you still need antibiotics afterwards in case there is bacteria in your bloodstream. We do not want that to go to your heart or other parts of your body and cause another infection. Same thing with cancer cells. We know if you have cancer somewhere in your body, the cancer cell could be in your bloodstream. We may not be able to measure it right now, but we want to make sure that that cancer cell does not land in your liver, lungs, brain, bones, and take up residence there. That is why we give these other treatments on top of the surgery.

How do you envision the role of genomic profiling evolving in the future of breast cancer?

I think we are on the precipice of this, and I think there is a lot more work that has to be done. We are finding more genes, finding new medicines that can work in the cancer cell or in conjunction with a treatment that we already have. One may have heard of CDK4/6 inhibitors. Those drugs can work in conjunction with the antiestrogen drugs and make those antiestrogen drugs work better. We will be drilling down more on cancer cells to find out what makes that cancer cell tick. What makes that cancer cell grow? Why does it proliferate? And those genes, I think, are going to be some of the things that we'll be focusing a lot of research on.

What are some best practices that you would recommend for oncologists who want to integrate genomic testing into their care for patients?

At least in breast cancer, the medical oncologists work with us all the time in a multidisciplinary way, meaning that we will have a press conference, and we all look at the patient's tumor. We look at the slides, we look at the images, and then we talk about which gene testing to get. Is it necessary? Will you be giving chemotherapy no matter what that gene testing says? There is an art to medicine. The beauty of genomic profiling is that it is another piece of information for us to make those decisions about. It is not just about genomic profiling. That is probably one of the most important things that medical oncologists and surgical oncologists deal with, is to know when to get that test and how to interpret that test.

There are some studies looking at patients and drawing their blood in the future to look for recurrences. There are multiple companies looking at this and multiple universities looking at this. There is so much change in our field, and we will be keeping up with this on a regular basis. I think that medical oncologists know that we have to work within the context of all of these tests, and we cannot just make it based on PD-L1 positivity or an oncotype.