Breast Cancer Diagnosis and Treatment
PHYSICIANS’ ROUNDTABLE
In this Physicians’ Roundtable, Eisenhower physicians discuss advancements in the detection and treatment of breast cancer and how the team at Eisenhower is working collaboratively to ensure the best experience and outcomes for their patients. The panel includes Vasudha Lingareddy, MD, FACRO, Board Certified in Radiation Oncology; Edgar Staren, MD, PhD, Board Certified in Surgery and specializing in Surgical Oncology; Paul Sylvan, MD, Board Certified in Radiology and Internal Medicine; and Manasa Vulchi, MD, Board Certified in Medical Oncology. The Eisenhower participants were joined by Lisa Madlensky, PhD, CGC, Genetic Counselor and Professor of Medicine, UC San Diego Health, who works with Eisenhower Health patients through Eisenhower’s affiliation with the UC San Diego Health Cancer Network. Justin Thomas, MD, Board Certified in Pulmonary Disease, Interventional Pulmonary Disease, Critical Care Medicine and Internal Medicine, moderated the discussion.
Dr. Thomas: How common is breast cancer in our country?
Dr. Staren: Very common. It is the most common cancer in women. One in eight women in the United States can be expected to develop breast cancer during the course of their lifetime.
Dr. Thomas: One in eight women. And what about in men?
Dr. Staren: It’s much less common, but one percent of breast cancers do occur in men.
Dr. Thomas: What are the signs and symptoms of breast cancer? What should women be looking out for?
Dr. Vulchi: Most early stage breast cancers are mammographically detected during screening. One of the symptoms to look out for is a mass, or lump, in the breast. Sometimes, skin changes like redness, thickening over the skin can be early signs, or other things like nipple inversion. In more advanced cases, palpable lymph nodes in the axilla [armpit] can be a sign of cancer as well.
Dr. Staren: Bloody and perhaps clear spontaneous nipple discharge may occur as well.
Dr. Vulchi: These are the signs for early stage or local regional breast cancer. If it’s metastasized, some of the signs we can see depend on where it has spread. If the cancer has spread to the lung, people can present with cough or shortness of breath. Sometimes we see pain in the lower back or bone pain if it metastasized to the bone.
Dr. Thomas: How important are self-breast exams?
Dr. Sylvan: Interestingly, the United States Preventive Services Task Force recommended against doing breast self-exam and clinical self-exam. They say there’s basically no evidence to support doing that, although we all know anecdotally that we see many women who have found their own breast cancer.
Dr. Staren: I agree with you, Dr. Sylvan. According to statistics, almost 40% of women come in because they felt something in the breast. Telling them not to pay attention to that seems counterintuitive. Part of it ends up being the importance of showing women how to do a breast exam. I’ve told patients the value of finding a time of the month where they examine themselves and actually draw a map of their breasts of what they feel. When they examine themselves the following month, they have something to compare to. If they find something radically different, it’s worthwhile bringing that to the attention of their physician.
Dr. Thomas: What is the survival rate of breast cancer? How has that played out in the past 10 years?
Dr. Sylvan: Between 1989 and 2020, there has been about a 43% decrease in deaths from breast cancer.
Dr. Thomas: What would you attribute that to?
Dr. Sylvan: I think it can be attributed to both earlier detection and improved treatment.
Dr. Staren: Today, about two thirds of patients will present with the disease limited to their breast and their five-year survival is well over 90 to 95%. It’s one of those circumstances where emphasizing the positives seems to be well worthwhile.
Dr. Thomas: Perhaps you can touch on the advancements of imaging for breast cancer, starting with mammography.
Dr. Sylvan: There has been quite a dramatic change over the years. Years ago, we went from xeromammography to film screen mammography, which was a significant improvement. In about 2000, the FDA approved digital mammography, which was a significant improvement over film screen mammography. In 2011, we saw the FDA approval of 3D mammography. About half of the mammography units in the country now are 3D. All three of our breast centers at Eisenhower have only 3D mammography.
In addition to mammography, we use other adjunct technologies to diagnose breast cancer, including ultrasound. The ACRIN 6666 trial was an interesting study looking at women who had undergone screening mammography and then adding an ultrasound in addition to the mammogram for three consecutive years. These were women with dense breasts, so, not a true screening population, as they were at somewhat higher risk for breast cancer due to the dense breasts. The increase in cancer detection with ultrasound in that trial was 4.3 additional cancers per thousand women screened. That may not sound like a lot, but mammography on average detects only about five cancers per thousand women screened. The number of cancers detected by ultrasound was almost equal to the number of cancers detected by mammography. The study included one further step, which was one MRI after three consecutive years of a negative mammogram and ultrasound. In this study 14.7 additional cancers per thousand women screened were detected by a single MRI. Additionally, we offer contrast-enhanced spectral mammography (CESM).
Dr. Thomas: Who qualifies for CESM?
Dr. Sylvan: It would be those in a high-risk population, defined by a lifetime risk of greater than 20% of developing breast cancer. It can also be very helpful for diagnostic work-ups and problem solving.
Dr. Thomas: I assume we have a dedicated team of breast radiologists who are dedicated to breast imaging.
Dr. Sylvan: Yes, we’re very fortunate. We have four dedicated breast imagers who do only breast imaging 100% of the time. Nothing else. You want to have people who are very experienced at this. Breast imaging is difficult and it requires a lot of experience to do it well.
Dr. Thomas: Besides having that experience, what are some of the other advantages of having a dedicated team of imagers?
Dr. Sylvan: In terms of working with the technologists and the rest of the staff, they don’t have to deal with 50 different radiologists who come in one day a month. The staff learns what the individual radiologists want, and the radiologists learn how to work with the nurses, technologists, and the rest of the team. We work closely on a daily basis with the surgeons, and with the medical oncologists and the radiation oncologists. The breast imagers and the breast surgeons have an incredibly close working relationship which is really important for all of us.
Dr. Thomas: Would you say it also shortens the time to diagnose these women?
Dr. Sylvan: I think it can shorten the time to diagnosis because we’re better at detecting subtle cancers earlier. And once a patient is found to have cancer, getting them to the appropriate surgeon, medical oncologist and radiation oncologist expeditiously is critical. We take a true team approach to the treatment of the patients.
Dr. Thomas: Let’s say you found something on mammography. What is the next step?
Dr. Sylvan: If there are calcifications on a mammogram, the patient will usually have a stereotactic biopsy. If there’s a mass or another finding such as architectural distortion, we will look with ultrasound first, because we would rather do the biopsy under ultrasound guidance. It’s easier and more comfortable for the patient and the procedure goes more quickly. If it’s a finding that is only seen on a mammogram, then we will go to stereotactic biopsy.
Dr. Thomas: Explain a stereotactic biopsy for our readers.
Dr. Sylvan: It’s a biopsy that is guided by the mammogram. It’s done on a specialized unit where we take a pair of stereotactic images, and the computer uses this information to generate exact coordinates of where the lesion is located in the breast. A specialized biopsy device is advanced to this location and we are able to retrieve tissue samples from that exact location.
Dr. Thomas: What types of breast cancer are there? Why is it important to distinguish between these different types of breast cancer?
Dr. Staren: I usually give an analogy of a tree and I draw the trunk of the tree coming from the nipple, and branching out into various branches or ducts. The lobules [glandular tissue], interestingly enough, look like leaves. I think it’s helpful for the patient to visualize where the cancer is originating from - the ductal origin, or from the lobules. The vast majority of breast cancers are from the ducts. The reason it’s important is while the principles of treating breast cancer are generally the same, there are certain characteristics unique to those tumors, which might amend the treatment recommendation. Lobular cancer is notorious for being difficult to examine thoroughly. All too often, we’ll get surprises in how much more extensive the lobular carcinoma can be. It doesn’t have the same characteristics and it doesn’t form micro calcifications, for example, so the imaging can really fool us with asymmetry.
In general, however, the treatment for both of these involves removal of a tumor with a margin of surrounding tissue that is free of cancer cells. That can be done with a lumpectomy or mastectomy. If a core biopsy does come back as atypical ductal hyperplasia, we recommend an excisional biopsy for those, because those patients end up having a higher risk for ductal carcinoma in situ [in place]. Ductal carcinoma in situ is not only an increased risk factor for the development of an invasive cancer, but needs to be treated in a more aggressive manner, somewhat similar to the way we treat invasive breast cancer.
I think it’s helpful to have a pathology discussion with the patients, ductal or lobular, fibrocystic versus non-fibrocystic, and invasive versus in situ. I believe they’ll be more prepared for a discussion on treatment if they better understand their specific diagnosis.
Dr. Vulchi: In regards to systemic treatment, we currently treat both invasive ductal and invasive lobular very similarly. There is ongoing lobular cancer research, because they can be more hormonally driven and less likely to respond to systemic chemotherapy. There are ongoing trials looking into that specific subtype to see if we need to treat them any different - for now, we treat both the same.
Dr. Thomas: Who would be a candidate for referred genetic counseling?
Dr. Madlensky: We use the National Comprehensive Cancer Network (NCCN) guidelines that are updated every year to determine who would be a candidate. These guidelines are published by high volume, academic cancer centers with ongoing research. Every year, these committees review all of the evidence that’s been published, as well as the research studies and clinical trials, to determine if any updates are needed to go into these guidelines.
When I started practicing in genetics nearly 30 years ago, the only way you would be able to access testing of the BRCA genes, or BRCA1 and BRCA2, would be if you had a really compelling family history. Now, it’s a completely different world and anyone who wants genetic testing, even if they don’t meet the current NCCN guidelines, can order it out of pocket for about $250. The NCCN guidelines currently recommend all women with breast cancer diagnosed before the age of 50 - family history doesn’t matter - are absolutely appropriate for genetic testing. Women who have the triple negative type of breast cancer, no ER, PR, or HER2 showing up on their tumor cells, of any age, are appropriate for genetic testing. Women who have been diagnosed with breast cancer after the age of 50 but have a family history of either ovarian cancer, pancreatic cancer, or other people in their family with breast cancer, may get genetic testing.
We’re very close to the point where almost all women with breast cancer are appropriate for genetic testing, and some clinics do offer testing to all women. It’s easier to describe who isn’t going to get a lot of information out of genetic testing - typically an older patient over the age of 80 with slow growing, not aggressive disease, who has a lot of female family members and they’ve all lived to an old age - and nobody’s had ovarian cancer or breast cancer. We look at the whole picture to see if the probability that this is a high risk mutation family is extremely low. Other than breast cancer, the guidelines for genetic testing include anybody with ovarian cancer or pancreatic cancer, regardless of family history.
Dr. Thomas: Are there other genes, besides the BRCA1 and 2, that play a role in breast cancer that we should be looking at screening?
Dr. Madlensky: In the last 15 years, we’ve learned there are other genes, other factors that increase the risk of breast cancer, but nowhere near to the extent of the BRCA genes. The most common one, by far, is a gene called CHEK2. This is a really tricky gene, in terms of management and recommendations, because even within this one gene, there are some mutations that increase risk enough to warrant more aggressive screening, for example.
However, there are other variations in this gene that barely move risk. So, even though somebody might do genetic testing and see on their report that they have a mutation, or a variant in this gene, it might not change their medical care. That’s one of the reasons we always recommend walking through those reports with a genetic counselor. We will look up the specific mutation and do a full family history. We take the patient’s breast density into account, any history of biopsies, plus other risk factors and protective factors. We do a personalized risk assessment and make recommendations, particularly for the non BRCA genes, where there’s a wide range of risks that could go along with those genes.
There are other genes, too - ATM, PALB2 - in the middle risk range. There’s a set of very rare genes that almost no one in the population has, that are diagnosed in childhood or in the teen years. That said, the most important genes to test for are BRCA1 and 2, CHEK2, ATM, and PALB2. Those are the five that are going to change care, most of the time.
Dr. Thomas: How would you counsel someone who has a BRCA mutation, but may have no history of breast cancer themselves?
Dr. Madlensky: For someone who tests positive, the most important thing that we take into account is age. Where are you in your reproductive years? If we find a 25-year-old who tests positive, the conversation is going to be very, very different, than a 70-year-old who tests positive. For a younger person, we take into account their family planning desires. Are they planning on having a family? If they’re at a young age, what is their breast density? Do they hope to breastfeed one day? There’s also the psychological aspect - why did they get tested and what is their family history? The biggest decision for women who have a high risk mutation such as BRCA1 or BRCA2, is to think about reducing future risk of ever getting cancer in the first place.
For that reason, bilateral mastectomies, with or without reconstruction, are certainly an option. The other option is not a risk reducing one, but a surveillance one, with the idea of monitoring more aggressively. That means alternating mammograms and MRIs every six months. The counseling approach helps women understand the difference between risk reduction and early detection. One of the most interesting survey findings I’ve ever seen was a National Health survey, and it asked women, “What’s the number one thing you do to reduce the chance of getting breast cancer?” And the answer was mammograms. Mammograms are not going to reduce your chance of getting breast cancer. They’re going to help you find it earlier.
We have a nuanced discussion about risk reduction versus early detection. Ideally, we set up referrals to a high risk clinic where patients can meet with a surgeon and talk about what’s involved in mastectomies. What are the pros and cons? For women who are considering surveillance, we want to make sure they’re being followed at a place that has all of the technologies mentioned by Dr. Sylvan, so they have that full array of screening opportunities. On top of that, we also talk about the increased risk of ovarian cancer. Unlike breast cancer, where we have really good screening and the ability to find breast cancers early, we don’t have any useful screening for ovarian cancer.
When there is an increased risk of ovarian cancer, the discussion is not if we’re going to recommend that your ovaries and fallopian tubes be removed, but when. What is the right age? That’s dependent on whether there was a BRCA1 or BRCA2 gene. Is there any other family or gynecologic history? Even though there are general guidelines, the emphasis I like to make is that this is a very personalized risk assessment, and anything we recommend is going to be dependent on age, family history, and all those other factors.
Dr. Thomas: Dr. Staren, tell us about the high risk breast clinic you’ll be heading at Eisenhower.
Dr. Staren: A high risk program is so much more than just assessing the risk. It provides screening, diagnostic and treatment options for a patient. In addition to the recommendations for mammography, MRI, etc., it should provide patients with education and genetic counseling, as well as mental health resources, spiritual care, social workers, and nurse navigators. We want to ensure these patients are properly ushered through this potentially devastating circumstance of being at high risk and potentially having a diagnosis of breast cancer. More than just assessing the patients for their risk, it provides an opportunity to provide a patient with a unique and thorough kind of management.
Dr. Thomas: Dr. Vulchi, how often are breast cancers caught in the early stage?
Dr. Vulchi: About two thirds of breast cancers are caught when they’re localized, meaning just in the breast and not spread to the lymph nodes. About a quarter of them are caught after they’ve spread the lymph nodes. With mammography and with the advances in imaging, it’s very rare to find metastatic disease at the time of diagnosis. It’s probably only five to 10%.
Dr. Thomas: So, screening plays a huge role.
Dr. Vulchi: Absolutely.
Dr. Thomas: What is radiation therapy and how does that work?
Dr. Lingareddy: Simply put, these are X-rays, but the beam is much more focused on whatever the target is. It’s going to cause DNA damage. Your normal cells should recover - most of them, anyway. But the DNA of any tumor cells left behind should be damaged to the point where they undergo tumor death and the body clears it, or they’re just not producing any additional cells.
Dr. Thomas: How does it fall into the treatment paradigm for breast cancers? Does everyone get radiation therapy?
Dr. Lingareddy: No. A woman who has an early stage breast cancer who opts for mastectomy would not necessarily need radiation therapy. Women with more advanced stage cancer, positive margins, positive lymph nodes, even though they’ve had a mastectomy, would require radiation therapy post-surgery. Anybody who undergoes breast conservation therapy, lumpectomy, plus or minus sentinel lymph node biopsy, would certainly want a discussion with the radiation oncologist about the benefit of postoperative radiation which will reduce the chance of the cancer recurring within the affected breast, but doesn’t necessarily always translate to survival. And that’s really the discussion to be had. Is this a young woman where the radiation therapy might actually improve her survival? Or is this an older woman with an unaggressive tumor, and although there may be a local control benefit to radiation, it would not impact her survival. In this case, we wouldn’t recommend putting her through radiation.
Dr. Thomas: How many radiation treatments are typically given?
Dr. Lingareddy: One of the best things to happen in breast radiation therapy is we’ve shortened the number of treatments.
Dr. Thomas: That’s great.
Dr. Lingareddy: Patients used to get six to seven weeks of radiation therapy and that’s definitely reduced. The majority of patients will receive a three-week course of radiation therapy, 15 to 16 treatments, Monday through Friday. Some patients will need an extra four or five treatments to the tumor bed, where the tumor used to be. That’s dependent on margin status, age, tumor aggressiveness and other factors. But the majority should fall into that three to four week time period.
Dr. Thomas: Dr. Staren, what are some of the advancements in breast cancer surgery over the last decade or more?
Dr. Staren: The surgical goal in treating breast cancer is essentially to remove the tumor with a margin of normal tissue. If that can be done safely by removal of just a portion of the breast, a procedure referred to as a partial mastectomy or lumpectomy, then it’s an option for the patient. There are still some circumstances when lumpectomy is not an option. This may include very large tumors, tumors which are diffusely located in the breast, patients with a previous history of breast or chest wall radiation, as well as other situations. This greatly demonstrates the need for a multimodal team. In the past, patients with large tumors would automatically be taken to the operating room for mastectomy, and now we have circumstances where those patients can receive chemotherapy prior to the surgery - so-called neoadjuvant chemotherapy.
Currently, about 40% of patients who would have had mastectomies end up being converted to patients who instead qualify for lumpectomy, a very exciting change in surgery over the last 10 or 15 years.
The other change that we take for granted because it’s been around for 20 years, is the dissection of lymph nodes in the armpit. A very significant number of those patients would develop arm swelling from lymphedema. Now, that’s rarely done.
Instead, we do a sentinel lymph node biopsy where a small amount of radioactive dye is injected into the breast. The dye transfers to the lower lymph nodes in the axilla, the so-called sentinel lymph nodes; we then use a radiation counter or gamma counter to detect that radiation and identify those sentinel nodes. When a patient is having a lumpectomy, we make a very small incision in the armpit and identify those nodes and remove them. That decreases the risk of fluid collection in the armpit and lymphedema substantially. If we’re performing a mastectomy, we can do it through the same incision as the mastectomy incision. So, it’s a very significant advantage to the patient.
For mastectomy patients, the reconstructive procedures have also had substantial advancement. Patients may be a candidate for immediate or delayed reconstruction and they may be able to have reconstruction with placement of an implant or with their own tissues. I will routinely have them see a plastic surgeon to make sure that they understand what would be involved.
Dr. Thomas: Tell us about MOZART 3D specimen imaging that you use during surgery.
Dr. Staren: The cooperation between the surgeon and the radiologist is very important. Routinely, we’ll have the ability to have the radiologist review a specimen mammogram; that is, a mammogram of the lumpectomy that’s removed to determine if the area that we’re suspicious of, or has been confirmed to be a cancer, is in fact removed. Having a radiologist confirm our diagnosis is very, very reassuring to the surgeon and an example of optimal care for the patient.
Dr. Thomas: Dr. Vulchi, what is the purpose of hormone therapy in breast cancer?
Dr. Vulchi: Hormone therapy means treating the patient with hormone blocker medications. About 70% to 80% of breast cancers express estrogen and progesterone receptors. All women, no matter their menopausal status, make some amount of estrogen in the body. When that estrogen sits on the receptors, it acts as a signal for the cancer cell to grow and divide. The hormone blocker medications prevent estrogen from getting to the receptors, either by reducing the estrogen production in the body or by blocking the receptor itself. We use hormone blockers after the patient has had their surgery, to prevent or reduce the risk of a recurrence either in the breast or in other parts of the body. We also use these medications in stage four or metastatic breast cancer to keep the cancer in check and reduce the chances of it growing.
Dr. Thomas: How has chemotherapy changed over the years for treatment of breast cancer?
Dr. Vulchi: The last time a cytotoxic chemotherapy was approved for breast cancer was in 2010. Since then, every medication that has been FDA approved has been targeted treatments like CDK4/6 inhibitors or PARP inhibitors, which work in patients with BRCA1, 2 mutations. We use other types of medications like immunotherapy in our triple negative breast cancer patients. The most exciting development is drugs called antibody drug conjugates and it’s a technology where we can deliver high doses of highly potent chemotherapy directly to the cancer cells. What has changed is the type of medications we use. We still use chemotherapy, but we are trying to move away from cytotoxic chemotherapy to more advanced delivery mechanisms.
Dr. Thomas: What is immunotherapy?
Dr. Vulchi: Our immune system should be capable of identifying foreign cells, and cancer is foreign to the body, but cancer cells develop a mechanism where they can evade immunity. Immune therapy uses medications that go into the body and retrain our immunity to identify the cancer and kill it. It’s a very sophisticated way of training our immunity.
It is important because people who have a pathologic complete response (pCR) do very well long-term and it’s about 65% with the addition of immunotherapy. Whereas in the past, the chemotherapies we were using produced a pCR rate of 45% to 50%. That’s a huge change and we know that pCR correlates with overall survival in a lot of situations.
We also use immunotherapy in the metastatic setting for some of our triple negative breast cancer patients. We now have data showing that it also works in estrogen driven breast cancers, higher risk lymph node positive situations. It has not been FDA approved yet, but the most recent phase three trial showed significant benefit. We’re waiting to see if the approval comes through.
Dr. Thomas: What non-medication interventions do you use in your practice?
Dr. Vulchi: We have an excellent support group led by our social workers and nurse navigators. We have exercise classes with yoga and tai chi, and we also offer meditation. We don’t have acupuncture in our clinic, but we have practitioners in our community we refer to.
Dr. Thomas: In closing, how important is teamwork in the diagnosis and treatment of breast cancer?
Dr. Vulchi: Having access to a good surgeon, a breast radiation oncologist, a good tumor board, and an excellent breast radiologist, all add up to really good patient care. I am really fortunate to be a part of this team.
Dr. Lingareddy: I agree with Dr. Vulchi. Additionally, it’s wonderful having Dr. Madlensky and her expertise. Our patients are very fortunate.
Dr. Sylvan: It is really an exciting time for us. We already had a great program, but we’re reaching new levels with the recent additions of Dr. Vulchi and Dr. Staren. Dr. Madlensky, I look forward to calling on you in the future. It was great having your input and expertise during this discussion. I learned a lot from you during this roundtable and I’m grateful you’re a part of our team.
Dr. Madlensky: Thank you. I appreciate that. As part of a multidisciplinary team, I learn so much from all the other specialties and from being a part of the tumor board. To a certain extent, I think we all do patient navigation. Patients are never going to ask questions that only apply to our area of expertise, so it’s great when I can give a response based on what I learn from this team. And to know to whom I should refer them for specifics. It gives patients more confidence knowing there’s such a wide range of experienced clinicians looking out for them.
Dr. Staren: In the very recent past, treating breast cancer was treating the tumor. We really didn’t differentiate as much between the patients. We had a couple of treatment modalities. But now, because of the expertise in multiple fields working together, I think it’s allowed us to evolve into treating the individual and recognizing that individuals differ radically and therefore our treatment and approach to taking care of the patient should be similarly sophisticated.
To learn more about the Breast Cancer Program, including breast cancer screening
services, visit EisenhowerHealth.org/Breast.
