Thursday, September 28, 2023
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Dr. Antonio Wolff: Today, we have a so-called "good problem" in breast cancer: Outcomes are improving, and women are increasingly surviving. Between improvements in diagnosis, earlier detection with more widespread use of mammography screening, and advances in treatment -- including a better understanding of how to tailor therapy to women with hormone receptor-positive vs negative disease -- most women with a diagnosis of breast cancer will survive their disease and go on to live full lives. Nevertheless, with these advances and increased survival have come new challenges, including weight, lifestyle, and fertility issues, as well as questions about who is the appropriate healthcare provider after active treatment ends. One of the main challenges for those of us who treat patients with breast cancer is how to facilitate our patients' integration back into life beyond breast cancer and specifically back into a more "normal" healthcare routine. For example, other healthcare professionals (ie, nononcologists), often tend to worry first and foremost about cancer recurrence -- while giving less attention to other important healthcare issues. Breast cancer survivors still need recommended cancer screenings, such as mammography and colonoscopy; they may be at risk for heart disease as they age, regardless of their breast cancer diagnosis; and they may have cancer-treatment-related complications, such as osteoporosis resulting from bone mineral loss.
One of the questions that is frequently raised centers on how intensive long-term follow-up care should be. How should breast cancer patients be followed and how frequently? Also, perhaps most basic, is the question of who should be following these patients? Anne, perhaps you could start by sharing the approach that you and your colleagues follow in Michigan.
Dr. Anne Schott: We recommend follow-up every 3 to 4 months for the first 2 years after completing adjuvant chemotherapy (ie, 3 or 4 times per year). At our institution, the surgeons have opted out of much of the follow-up for women who receive systemic therapy, except for perhaps one post-op visit. So these patients see either the medical oncologist exclusively or, if they had medical therapy in addition to radiation therapy, they alternate back and forth, seeing the medical oncologist twice a year and the radiation oncologist twice a year.
In terms of follow-up testing, we order annual mammography or whatever breast screening is indicated for that individual. We don't routinely recommend blood testing, other than to follow-up on toxicity associated with any ongoing therapies, such as annual liver function tests in women on tamoxifen.
We don't recommend screening CTs [computed tomography] or PET [positron-emission tomography] scans in asymptomatic individuals (explaining this to the patient is always a difficult conversation). For women who are on aromatase-inhibitor therapy and need bone density screenings, we take an active role. We order the test through our own clinics because it's not always routinely done through the primary care physician. Finally, we recommend Pap smears and colonoscopy screenings for women who are candidates -- but we don't typically initiate the ordering or perform the Pap smears. We do ask that patients go to their primary care physicians or gynecologists for those screening tests.
Dr. Wolff: Jennifer, what has your experience been at Dana-Farber? Is your approach similar to or different from Anne's in Michigan?
Dr. Jennifer Ligibel: We have also worked to coordinate follow-up care for our breast cancer patients, although our approach does differ somewhat from the University of Michigan plan. Our surgeons often remain involved in follow-up care, especially for women who have undergone breast-conserving surgery. Patients generally see their surgeons once yearly, and the surgeons generally coordinate mammograms and other breast imaging. Patients also follow-up with their radiation oncologists for the first year after diagnosis, if applicable. Finally, patients who receive chemotherapy and/or endocrine treatment are followed by medical oncologists.
In the first year after breast cancer diagnosis, patients are seen every 3-4 months, alternating between the involved subspecialties. After this period, they generally see the surgeon once a year at the time of their mammograms and the medical oncologist every 6 months.
There is currently some debate regarding the optimal follow-up for patients after 5 years. With the prolonged use of endocrine therapies beyond 5 years, we now tend to follow patients with estrogen-receptor (ER)-positive disease on a yearly basis for as long as they remain on therapy.
Dr. Wolff: Another question that often comes up concerns the necessity for surveillance tests in otherwise-asymptomatic patients. Are there blood tests or tumor marker surveillance tests that might be indicative of early metastases? What about the often controversial question of imaging surveillance with bone scans, CT scans, and FDG [F-fluorodeoxy-D-glucose]-PET scans?
Here at Johns Hopkins University, our group has adopted the ASCO guidelines,[1] which recommend against any surveillance blood testing or imaging studies in an otherwise-asymptomatic patient with a normal clinical exam. But in conversations with medical oncologists who do not exclusively see breast cancer patients like we do, I hear that patients want to have a piece of paper with a normal test result, to have some reassurance of a clean bill of health. Indeed, for doctors who also treat diseases like lung and colon cancer, ordering imaging studies for surveillance on a routine basis a few times a year is standard. It may not be clear that these strategies do not translate to breast cancer. The other argument I have heard is that it is harder for small or solo practices than it is for large academic institutions to follow recommended guidelines in terms of not ordering tests. With all that in mind, I'm wondering what has been your experience regarding surveillance tests for breast cancer?
Dr. Schott: We are more comfortable in the academic centers with the no-testing recommendation. We've all had experiences where patients transfer their care to us from the community where they've had routine tumor markers, CT scans, or PET scans, and it becomes a long conversation to explain why we don't do it. It's uncomfortable to explain that the reason we don't test is because such tests won't detect early, curable disease. Often, patients -- particularly at that vulnerable time when they've just finished their adjuvant therapy and are asking about the follow-up plan -- find it very difficult to hear that. But I think it's still necessary to have that conversation -- and I think it's appreciated in the long run.
Dr. Wolff: Another question is whether you see value in stratifying the frequency of visits based on initial stage -- ie, if a patient with an early-stage, HER2-positive tumor may be seen less frequently for follow-up than someone with a locally advanced, HER2-positive tumor.
Dr. Schott: I think you're asking whether risk of disease recurrence or the intensity of therapy affects frequency of follow-up. In my experience, the need to see the oncologist isn't just about the risk: It's still about the reality of and dealing with having had a breast cancer diagnosis. I think in practice, we do end up tailoring the number of visits somewhat, but it actually has more to do with the comfort level of the patient as a survivor. In other words, if I see a patient who is doing extremely well, I might suggest waiting 6 months before our next visit, and then I'd ask how she feels about that. If she jumps at the chance, then I'm good with that because the visit isn't really for me, it's for her. So I stratify less on disease stage than on how patients are doing, although I admit I may be more likely to recommend follow-up earlier than 6 months for some patients, even with earlier-stage disease.
Dr. Ligibel: I definitely agree with Anne. I think that follow-up visits serve many purposes, including providing ongoing emotional support for patients. Those with more-advanced disease have more frequent visits during active therapy, but over time, these patients are seen on a similar schedule as patients with earlier-stage disease.
Dr. Wolff: Jennifer, after completion of local therapy, do your patients -- who have been seeing the surgeon and radiation oncologist -- also see the medical oncologist?
Dr. Ligibel: After the completion of local therapy, most patients are followed primarily by the surgeons and the medical oncologists, with the surgeons seeing the patients once a year and the medical oncologists seeing the patients twice a year. There are some exceptions to this routine. The surgeons usually will not follow patients who have undergone bilateral mastectomy, and the medical oncologists do not consistently follow patients with DCIS or early-stage cancers who are not treated with either chemotherapy or endocrine treatment.
Dr. Wolff: Let's expand on the role of the primary care provider, and by primary care provider, I want to include not only the internist but also the gynecologist and the nurse practitioner, who oftentimes function under the supervision of an internist. As we have established, early on in treatment, patients may be accustomed to seeing several specialists. But as time moves on, they're not seen as often. At this point, the question of transition from the cancer specialist to the non-cancer specialist comes up. It can be tricky, especially in our fragmented healthcare system and particularly with younger patients who may not have a primary care provider. At Johns Hopkins University, we have been trying to implement a "shared-care" model, where we bring in the primary care provider early on, soon after completion of locoregional therapy and any chemotherapy. Jennifer, what do you do at Dana-Farber to involve the primary care provider?
Dr. Ligibel: In Boston, as in many places, we have a bit of a primary care shortage at this point, so this can be a difficult issue. One approach we're starting to pilot involves having a specific primary care group that works closely with us. We then steer our patients who don't already have a provider toward that practice. For patients who have established primary care doctors, we've been working on developing an end-of-treatment summary that outlines the patient's treatment and discusses potential short- and long-term complications of the therapy. We also make sure that primary care providers receive all the relevant notes and test results. We especially concentrate on looping the primary care physicians back in as patients finish their primary therapy. Many patients aren't in contact with their primary care physicians during their intensive breast cancer treatment, so we think that the completion of that regimen is a good time to put the patients back in touch with their primary care physicians.
Dr. Wolff: Anne, I'd also like to hear your thoughts about transitioning to a primary care provider. In addition, could you touch on a related subject that I have experienced personally, which is a possible discomfort on the part of the primary care provider about working with cancer patients? Interestingly, internists are often quite comfortable taking care of uncomplicated issues related to cardiology, and they don't necessarily refer their cardiac patients to cardiologists or their diabetes patients to an endocrinologist. But I have found, at least in the past, some reluctance or concerns about caring for cancer patients. I think this might be changing, as a new, increasingly educated generation of internists sees a growing number of patients who have survived their cancer diagnoses. Still, I'm wondering if you have experienced any reluctance on the part of internists, and if so, do you have any suggestions for how best to work with primary care providers?
Dr. Schott: Yes, I have experienced this reluctance. About 10 years ago, we established a service within the cancer center, called the Breast Wellness Clinic, to address the issue of patients (either on their own or led by their primary care providers) not wanting to let go of their subspecialty follow-up. At that time, we established a nurse practitioner-led clinic for patients who were more than 5 years out. In this clinic, patients are able to see someone who participated in their cancer care on an annual basis for clinical exam and breast imaging. It allows them to stay in touch with what is going on in breast cancer, so they can be reassured they aren't missing any new developments. This actually turned out to be very helpful when extended endocrine therapy became the norm, because we were able to identify a good number of patients who were candidates for extended endocrine therapy through their continued contact in our Breast Wellness Clinic.
The other thing that we do very early on is set up the framework for future care, including breast cancer follow-up and expectations for the primary care provider, such as cholesterol tests, bone density tests, Pap smears, and colonoscopies.
With this approach, you have to be prepared to communicate with the primary care providers to make sure they are available for follow-up. Although we offer long-term follow-up in our clinic, if the patient feels that her primary care physician is competent to do her breast care follow-up and is comfortable with that, then by all means we encourage her to stay with her primary care provider. Still, I would say that more than half the women, at least for some time, prefer to have an annual visit with their nurse practitioner in the breast clinic.
Dr. Wolff: Of those who choose the nurse practitioner, do the annual visits continue indefinitely, or do patients move on after a while?
Dr. Schott: I haven't checked the numbers, but my sense is that the majority continue follow-up at least for 5 years, with a slow decrease over time as women become more comfortable with not coming in to see the specialist. I think there are practical considerations, like distance traveled and insurance coverage, that also play a role in the decision about whether to stay in long-term follow-up.
Dr. Wolff: Thank you. I think there are 2 key messages here:
1. The importance of the early discussion, with expectations defined about the role of the cancer specialist in long-term follow-up vs the role of the primary care provider, as well as the importance of establishing a relationship with a primary care provider. 2. The importance of the transition out of the cancer clinic setting -- to emphasize to our patients that they are not being discharged, and we are not "cutting the umbilical cord." Rather, we're emphasizing the fact that they don't need to see us very often anymore, as well as the importance of having a good relationship with another physician who will watch their mammograms, do breast exams with some frequency, etc. Patients should be assured that we'll continue to be their doctors, and if they have any questions, they can call us and come back to see us. In my experience, patients have been reassured by this, and many are happy with the idea that it is okay to, if possible, forget a little about their breast cancer diagnosis.
To move on to another topic I'm often asked about: Is there anything else a patient should be doing to prevent recurrence? This question usually centers around diet and exercise. Weight management has become so topical, if you will, especially in a society where we have an obesity epidemic, and in fact a lot of breast cancer patients have a tendency to gain weight. Jennifer, how often do you hear these kinds of concerns from patients, and what recommendations do you think we should give them? Also, could certain lifestyle interventions have an effect on long-term breast cancer survival?
Dr. Ligibel: Regarding your first question, I don't think I go a day where I don't have patients complaining about the weight they've gained. Indeed, weight gain is very common in women after breast cancer diagnosis. Studies have shown that it is most common in women who are treated with chemotherapy, and especially in women who undergo menopause as a result of their treatment. However, weight gain has been described in some trials even in women who are treated with surgery alone for DCIS. Weight gain of up to 20 pounds in the 2 years following cancer diagnosis is not uncommon. Weight is clearly a big issue.
A lot of observational data suggest that women who are overweight or obese at the time of breast cancer diagnosis have an increased risk of cancer recurrence compared with leaner women.[2] There's also preliminary, though inconsistent, evidence suggesting that weight gain after diagnosis may be associated with a higher risk of recurrence.[3,4] Although more than 50 observational studies have looked at the relationship between body weight and cancer recurrence, there is currently no direct evidence that weight loss after diagnosis will reduce recurrence risk. The ongoing Lifestyle Study for Adjuvant Treatment of Early Breast Cancer (LISA) is the first randomized trial to look at the impact of weight loss on cancer outcomes. The trial will randomize more than 2000 postmenopausal women with early breast cancer to a weight loss program or a control group, and should provide important information regarding the impact of weight loss upon breast cancer prognosis.
There haven't been any randomized, intervention trials that looked at whether losing weight after diagnosis makes a difference. We do have a good, ongoing lifestyle intervention trial that will address the subset of postmenopausal patients being treated with an aromatase inhibitor, but there's not a lot of direct evidence at this point that weight change makes a difference in terms of breast cancer recurrence risk. However, I think that there is certainly very strong evidence that excess weight and weight gain after breast cancer diagnosis is associated with higher risk of heart disease and other adverse health outcomes, such as diabetes. And observational studies have suggested that women who are heavier have higher risk of breast and other cancers. These are all issues I discuss with my patients when we're talking about weight gain.
In general, weight loss and weight maintenance often require changes in diet and exercise patterns, and studies have looked at the relationship of both diet and exercise patterns to breast cancer outcomes. There is a growing body of observational data suggesting that women who exercise after breast cancer have a lower risk of cancer recurrence, even if they do not lose weight as a result of their activity.[5-8] However, there is currently no direct evidence that increasing exercise after diagnosis will lower the risk of breast cancer recurrence. In contrast, 2 randomized trials have examined the impact of dietary change on breast cancer outcomes. The Women's Interventional Nutrition Study (WINS)[9] randomized breast cancer survivors who consumed a high-fat diet at baseline to either a low-fat dietary intervention or an educational control group. There was a trend toward fewer recurrences in the low-fat diet group, and an unplanned subgroup analysis demonstrated a significant reduction in mortality in women with ER-negative cancers randomized to the diet group. The Women's Healthy Eating and Living (WHEL)[10] study randomized early-stage breast cancer patients to either a control group or to a dietary intervention that sought to decrease fat intake, as well as increase intake of fruits and vegetables. Unlike WINS, there was no difference in recurrence rates in the control and diet arms. Given these somewhat contradictory results, I think it is a little early to recommend a specific diet to breast cancer survivors.
With this inconclusive evidence, it can sometimes be difficult to know exactly what to tell breast cancer survivors. I generally recommend that patients engage in at least a modest amount of physical activity after diagnosis. The observational studies suggest that patients who engaged in moderate activity, such as brisk walking for at least 3 hours per week, had a better prognosis compared with inactive patients, so I generally recommend at least this amount of activity. I also recommend modest weight loss for patients who are overweight or obese and avoidance of weight gain for leaner patients. Finally, I generally recommend a balanced diet, but do discuss the results of the WINS trial and don't encourage carbohydrate-restricted diets like Atkins for breast cancer survivors, especially those with ER-negative tumors.
Dr. Wolff: Anne, any additional thoughts on the issue of diet and exercise?
Dr. Schott: It has been my observation that patients focus on what "more" they can do: what supplements they can take, what breast screenings they can have, what new breakthrough drugs are available. My answer to them is, as Jennifer said: low-fat diet, exercise, and vitamin D. I think these answers are sometimes disappointing to the patient because they're not as sexy or additive as a recommendation for a supplement or drug.
Dr. Wolff: To expand on that point for a moment: Although human nature wants a magic bullet -- a pill for cholesterol or for weight -- the reality is that what you must do -- diet and exercise -- requires hard work. We must educate our patients to be skeptical of grandiose claims (for example, some of the nutritional supplements that are marketed with little oversight) for interventions that have little or no evidence to support them.
My final question has to do with issues of fertility. Anne, I'll start with you, as you have had particular interest in these issues. The systemic therapies, including chemotherapy, tamoxifen, and the aromatase inhibitors, all have an impact on fertility. What are some of the concerns of your younger, premenopausal patients, and what do you tell them?
Dr. Schott: Patient concerns and our recommendations depend both on what treatments the patient requires, and her age. For example, I just saw a 28-year-old patient in follow-up. She was 24 at the time of diagnosis and was just getting married. Her disease stage required anthracycline- and taxane-based chemotherapy and hormonal therapy. She definitely wanted to be able to get pregnant following her breast cancer therapy, so the discussion covered the likelihood of not being able to conceive after chemotherapy, as well as the implications of forgoing chemotherapy or shortening the duration of hormonal therapy. In this case and similar ones, we can offer young women an opportunity for oocyte cryopreservation or in-vitro fertilization and embryo cryopreservation. Although these procedures are available, they are not widely used in the breast cancer population for a number of reasons, such as the time it takes to have the procedure done, which delays therapy, and the high cost, which is not typically covered by insurance.
The literature suggests that most young women in their 30s who receive chemotherapy do not become menopausal, and that the type and dose of chemotherapy used is an important risk factor for ovarian failure. For example, cyclophosphamide is associated with a higher risk of ovarian failure than taxanes, and it may be possible to design regimens without this drug. There are also strategies being tested right now, such as LHRH-agonists for ovarian protection, which may further decrease the likelihood of female infertility. Fertility discussions must be individualized.
Dr. Wolff: Anne, how often do you recommend that your young premenopausal patients consult with a fertility specialist? Or, since this is patient-driven, how frequently do your patients see a fertility specialist?
Dr. Schott: Consultation with a fertility specialist is offered to virtually any premenopausal woman who wants it. The outcome of the consultation will be very different depending on the individual situation. It may turn out to be reassuring, especially when the planned therapy isn't expected to have a big impact on fertility. We're fortunate to have this service available for all women who are newly diagnosed in our clinic.
Dr. Wolff: Jennifer, how do you and your colleagues in Boston approach these patients?
Dr. Ligibel: We have a young women's program, which is a sort of virtual clinic because we all continue to see young women in our practices. The virtual clinic identifies young women before they come in for their first appointments and sends them material about fertility and other aspects of breast cancer care in young women. A gynecologist, a high-risk obstetrician, and several fertility specialists work with the program, so that if women have specific questions, we can easily refer them to one of these providers. We do try to facilitate that because, again, a lot of these things are very time-sensitive. Many times young women present with aggressive disease, and there is a reluctance to delay therapy. That is why we try to start communication even before the first consultation with the medical oncologist.
Dr. Wolff: Before we wrap up, I'm wondering if either of you has any other concerns you would like to address?
Dr. Schott: I have 1 question. I'm curious as to whether your clinics have developed a policy on vitamin D deficiency at the time of diagnosis.
Dr. Wolff: That's a very topical and controversial question. One could argue, breast cancer aside, that we should implement vitamin D surveillance for bone health itself. But whether there's a direct benefit with regard to breast cancer, only time will tell.
Dr. Ligibel: I do think it's probably too early to make any definitive statements about the impact of vitamin D on breast cancer recurrence. There have been mixed data regarding the impact of vitamin D levels on breast cancer risk, and the Women's Health Initiative recently reported no decrease in breast cancer risk in women randomized to aggressive vitamin D supplementation.[11] Of note, there have also been some data from this trial suggesting that levels of supplementation do not correlate with serum levels of vitamin D, which implies that genetic or other factors may play a major role in determining serum vitamin D levels.[12]
There has been 1 observational study suggesting that vitamin D levels at the time of diagnosis are related to prognosis.[13] This is a very interesting finding and certainly warrants more investigation, but I think it is a little early to be telling women that taking vitamin D will lower their risk of cancer recurrence. There is also a lot of ongoing debate about the optimal level of vitamin D. We do recommend vitamin D supplementation to all of our patients for bone health, and we do discuss the recent study suggesting that vitamin D could be related to prognosis, but we are not routinely measuring vitamin D levels at this point.
This activity is supported by an independent educational grant from Susan G. Komen for the Cure.
