Although preventive therapy can reduce breast cancer risk in patients with lobular carcinoma in situ (LCIS) or atypical hyperplasia, most patients choose not to undergo such therapy. Clinicians at The University of Texas MD Anderson Cancer Center have developed a program to educate patients with LCIS or atypical hyperplasia about the importance of preventive therapy and encourage them to take this critical step to reduce their breast cancer risk.
Without intervention, women with LCIS or atypical hyperplasia are at least four times as likely as women without the conditions to develop breast cancer in their lifetimes. Hormonal therapy with tamoxifen or raloxifene can reduce this risk by 75%.
“Primary care physicians can prescribe these medications and follow up women in their clinic,” said Abenaa Brewster, M.D., M.H.S., a professor in the Department of Clinical Cancer Prevention and medical director of the Nellie B. Connally Breast Center. “Or physicians who do not feel comfortable prescribing these medications can refer their patients to a high-risk clinic.”
One such high-risk clinic is MD Anderson’s Cancer Prevention Center. But even here, Dr. Brewster, along with colleagues including Therese Bevers, M.D., a professor in the Department of Clinical Cancer Prevention and medical director of the Cancer Prevention Center, found that less than half of patients with LCIS or atypical hyperplasia were opting for preventive therapy. The clinicians developed a program to increase the use of preventive therapy by making sure patients understand the benefits of preventive therapy and ensuring that physicians strongly recommend such therapy.
When used for breast cancer prevention in women at high risk of the disease, tamoxifen or raloxifene is typically given for 5 years. Tamoxifen is approved for use in both pre- and post-menopausal women, whereas raloxifene is approved for use only in postmenopausal women.
Most women who receive tamoxifen or raloxifene experience no adverse effects. However, both drugs can cause menopausal symptoms, such as hot flashes, and the rare but more serious side effect of blood clots—specifically, deep venous thrombosis or pulmonary embolism. Tamoxifen, but not raloxifene, also increases the risk of uterine cancer.
“Patients and physicians need to think about the pros and cons of taking these drugs and decide whether they are favorably balanced,” Dr. Bevers said. “Some patients and physicians worry about the increased risk of uterine cancer with tamoxifen, but it’s a numbers game. We’re going to cause only a handful of uterine cancers while we prevent many more breast cancers. In women with LCIS or atypical hyperplasia, absent an absolute contraindication like a previous blood clot, the risk reduction is so large that it far outweighs the potential harms of the drug.”
Making a strong recommendation
The benefits of preventive hormonal therapy so outweigh its risks that the National Comprehensive Cancer Network guidelines call for physicians to strongly recommend such therapy for women with LCIS or atypical hyperplasia. However, despite these guidelines, only 20%–30% of women with LCIS or atypical hyperplasia in high-risk clinics receive preventive therapy.
“Physicians have been explaining the risks and benefits and then leaving the decision up to the patient,” Dr. Brewster said. “Of course, the patient makes the final decision about any treatment, but it makes a difference if the physician says, ‘I strongly recommend that you take this.’”
Drs. Brewster and Bevers and their colleagues developed a program to ensure that MD Anderson patients with LCIS or atypical hyperplasia receive a strong recommendation for preventive therapy. To make certain that the message was clearly delivered and understood, both providers and patients were surveyed about the strength of the recommendation after each clinic visit. In addition, an audit system was put in place to track the proportion of patients who received prescriptions for tamoxifen or raloxifene, and each provider was given quarterly feedback about his or her prescribing pattern.
The program has had the desired effect. At the initiation of the program in 2015, a survey of MD Anderson patients with LCIS or atypical hyperplasia showed that only 44% had received or were receiving preventive therapy. But between 2015 and 2017, 82% of such patients received prescriptions for preventive therapy. And among the patients who received the prescriptions, 76% of newly diagnosed patients and 48% of previously diagnosed patients were adhering to the therapy at 6 months. “The discrepancy between newly and previously diagnosed patients was an interesting finding that taught us that patients have to really buy into preventive treatment from the beginning,” Dr. Brewster said.
The program has been expanded to all of MD Anderson’s Houston-area locations where patients with LCIS or atypical hyperplasia are seen. “These are high-risk lesions,” Dr. Bevers said. “We should be helping women to understand the significant benefits of preventive treatment, and we should be saying we strongly recommend it.”
Brewster AM, Thomas P, Brown P, et al. A system-level approach to improve the uptake of anti-estrogen preventive therapy among women with atypical hyperplasia and lobular cancer in situ. Cancer Prev Res (Phila). 2018;11:295–302.
Regardless of whether patients with LCIS or atypical hyperplasia undergo preventive therapy, they should undergo breast cancer screening more frequently than women at low risk for the disease do. In most cases, this screening includes a clinical examination every 6 months plus mammography and magnetic resonance imaging alternating every 6 months. Physicians can access MD Anderson’s clinical practice algorithms for screening and risk reduction for breast and other cancers at http://bit.ly/2FLwonH.
Clinic Diagnoses Breast Lesions
The sole focus of the Undiagnosed Breast Clinic in MD Anderson’s Cancer Prevention Center is to detect and accurately diagnose breast cancer. The clinic provides consultations and second opinions for patients with breast symptoms such as lumps, swelling, redness, nipple discharge,
or abnormal findings on mammography or other imaging studies.
Patients seen in the clinic undergo a thorough examination with a review of their medical history. In addition, any outside pathology specimens and imaging studies are reviewed by a multidisciplinary team of cancer detection specialists, pathologists, and/or radiologists.
“If the lesion has previously been biopsied, we review the pathology to see if we concur with the diagnosis,” Dr. Bevers said. “For LCIS and atypical hyperplasia, we typically talk about how extensive the proliferation is on the pathology slides—does it only involve one or two terminal ductal lobular units, which we consider a limited amount, or is it more extensive? An additional consideration in a high-risk lesion is whether the neoplasia was associated with the targeted lesion or was an incidental background finding in the pathological specimen. We also want to make sure that more than 50% of the lesion has been sampled, so a review of the pre- and postbiopsy mammograms with our breast imaging team is critical.”
Needle or excisional biopsies may be ordered for patients whose lesions have not been biopsied or for whom an additional biopsy is required. In some centers, women with abnormal lesions such as LCIS or atypical hyperplasia routinely undergo excisional biopsy to rule out ductal carcinoma in situ or invasive breast cancer; however, only certain patients at MD Anderson undergo excisional biopsy. “If the lesion has been well sampled and the LCIS or atypical hyperplasia is limited or incidental, excision is commonly not recommended. This decision is made in our weekly multidisciplinary conference for the management of benign breast lesions.” Dr. Bevers said. However, she added, if less than half of the lesion was sampled or the proliferative lesion was extensive (i.e., more than three terminal ductal lobular units), an excisional biopsy would be recommended to make sure no cancer was missed owing to sampling error.
Additional biopsies and imaging studies, when needed, typically are done the day of the patient’s initial visit. Dr. Bevers said that every effort is made to get information to the patient as soon as possible. “We’re often able to give an indication of our level of concern based on our workup the same day,” she said. “It’s reassuring for women when we’re able to answer some of their questions at the end of the day. There’s less fear of the unknown, so they can start to formulate a plan and know what the next steps in cancer treatment, screening, or preventive therapy will be.”