Chemoprevention for Breast Cancer: A 'Big Ask' of PCPs

Veronica Hackethal, MD

September 18, 2019

Earlier this month, the US Preventive Services Task Force (USPSTF) issued updated recommendations for use of preventive medications in women at increased risk of breast cancer.

The recommendation is for asymptomatic women age 35 years or older who are at increased risk for breast cancer (and who have a low risk for side effects) to be offered chemoprevention with tamoxifen, raloxifene, or aromatase inhibitors.

"The recommendation is relevant to physicians providing preventive healthcare," said Heidi D. Nelson MD, MPH, professor at Oregon Health & Science University's School of Medicine in Portland, and lead investigator of the systematic review conducted by the USPSTF to draw up the recommendations.

"Assessment and discussion about risk-reducing medications can occur during the well-woman preventive care visit," Nelson told Medscape Medical News.

The hope is that primary care doctors, internists and gynecologists will act on these recommendations and spare the women who are treated from having to see an oncologist in the future.

But that hope has yet to be realized.

Although an estimated 10 million women in the US may be eligible for breast cancer chemoprevention, fewer than 10% of eligible women take such drugs.

Why the Lag in Uptake?

One reason for the low uptake is that having primary care doctors provide chemoprevention for breast cancer may be a lot to ask, given their other clinical responsibilities.

"Although I think that primary care doctors can absolutely counsel women about these medications in their primary care clinics, I agree that it's a big ask," Lydia Pace, MD, MPH, Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News by email.

Pace and colleague Nancy L. Keating, MD, MPH, also from Brigham and Women's Hospital, wrote an editorial in JAMA in response to the new recommendations.

Pace is a primary care doctor who works in a breast clinic for women at high risk for breast cancer. In that capacity, she has more time to focus visits on just one problem.

Many primary care doctors care for a large number of patients with a variety of health problems, and she doubts they would have the same luxury.

"I suspect that the most important role of most primary care providers is assessing women's risk, identifying women who might benefit from discussing risk-reducing medications, referring those patients to a specialist for that discussion, and perhaps following up with women after they've started chemoprevention," Pace said.

Yet another reason for low uptake is possible reluctance to prescribe cancer drugs. Primary care providers may perceive these drugs as heavy hitters with many side effects, according to Mary Daly, MD, PhD, oncologist at the Fox Chase Cancer Center in Philadelphia, Pennsylvania. She and Fox Chase colleague Eric Ross, PhD, authored a JAMA Oncology commentary responding to the USPSTF recommendations.

"I think some doctors feel a little intimidated by prescribing chemotherapy drugs," she said.

Lack of familiarity may also contribute.

"When you think about it, there are no more risks [with these drugs] than high blood pressure drugs or any other drugs that primary care doctors are used to prescribing," she added.

How to Assess Risk of Breast Cancer?

Another reason for the poor uptake is likely the complex decision process that starts with evaluating a woman's risk for breast cancer.

The new USPSTF recommendations expand the combination of risk factors for breast cancer that clinicians should consider, but fall short of providing definitive guidance about how to assess risk.

"The recognition that multiple risk factors may influence a woman's risk for breast cancer places a heavy burden on clinicians to interpret the benefits and risks for each woman," write Daly and Ross.

Unfortunately, current breast cancer risk prediction tools are confusing and difficult to use in clinical practice, Daly told Medscape Medical News.

One such tool is the Gail model, which has relatively few risk factors and is fairly easy to use. But recent models have become increasingly complicated, with multiple risk factors like BRCA1/2 status, breast density, alcohol use, diet, and exercise, making them harder to apply in clinical practice. Using these takes time that providers may not have.

"You have to do a good history for each woman about the factors that will affect the risks and benefits of these types of drugs. In modern day medicine, we often don't have that kind of time to spend," Daly said.

Moreover, the USPSTF does not endorse any particular risk prediction tool.

The recommendations mention that the National Cancer Institute Breast Cancer Risk Assessment Tool and the Breast Cancer Surveillance Consortium Risk Calculator may be useful. However, the recommendations add that current tools have low accuracy, and more research is needed to improve methods of assessing risk for breast cancer.

"Most methods perform only slightly better than age alone as a risk predictor," Nelson told Medscape Medical News.

What's more, no single cutoff for risk exists, although the task force says that women with at least a 3% increased risk for breast cancer in the next 5 years may benefit from chemoprevention.

That leaves clinicians in a quandary, and help might not be coming anytime soon.

"You're always uncertain talking to a woman about whether she's going to be one of the ones to develop breast cancer. I wish it were better, but that's how it is," task force member Michael Barry, MD, from Harvard Medical School, Boston, Massachusetts, said in a JAMA audio interview.

Patient Reluctance

Last but certainly not least: patients may be reluctant to start a 5-year course of therapy if they feel that the benefits do not outweigh the harms.

In the US, roughly 1 in 8 women will be diagnosed with breast cancer at some point in her life. Risk is higher for women with BRCA1/2 mutations, and for black women, who are more likely to die from breast cancer than women from other racial/ethnic groups.

However, not all women who are at increased risk for breast cancer actually develop it. This uncertainty, combined with a relatively small decrease in absolute risk with chemoprevention, makes for tricky decision making.

Evidence suggests that chemoprevention may decrease the risk of invasive breast cancer by up to 50%, but the absolute benefit is less: about 1000 women would need to take these drugs for 5 years to prevent invasive breast cancer in 7 of these women, according to the systematic review.

Also, although chemoprevention reduces the risk of developing breast cancer, studies have yet to demonstrate a mortality benefit.

The risk reduction may not offset worry about side effects. Both tamoxifen and raloxifene can increase the risk of blood clots. Tamoxifen has been linked to cataracts and endometrial cancer. Aromatase inhibitors have been associated with musculoskeletal and gastrointestinal issues, as well as adverse cardiovascular effects, though evidence is more limited for these drugs. Plus, as all of these medications decrease estrogen levels, they can cause menopausal symptoms like hot flashes.

Given uncertainty over benefits vs harms, the updated recommendations are consistent with past guidelines that emphasize the one-size-does-not-fit-all approach.

"The bottom line is that the right drug depends a lot on a woman's risk for side effects," commented task force member Barry.

For example, tamoxifen, a more effective drug, may be an appropriate choice for a woman who has had a hysterectomy and no history of clotting problems.

The task force also acknowledges that more research is needed on long-term outcomes among highest-risk women.

"Future research to identify optimal candidates for risk-reducing medications should focus on women most likely to benefit, including women with pathogenic BRCA1/2 mutations, strong family histories of estrogen-receptor positive breast cancer, and those with previous high-risk breast biopsies, such as atypical hyperplasia," Nelson said.

Amid the confusion, one theme emerges: the need for informed decision making, and a personalized approach.

"The major theme from my experience counseling patients about breast cancer risk and risk-reducing medications has been that every woman has a different perspective or preference regarding whether or not to take them, and the decisions are not easy ones," Pace told Medscape Medical News.

"Not all women choose to try them, and that is okay," she added.

Nelson has disclosed no relevant financial relationships. Ross reports grants from the National Cancer Institute and has a patent pending about methods for screening for muscle-invasive bladder cancer using responsiveness to neoadjuvant chemotherapy. Pace and Keating have disclosed no relevant financial relationships.

JAMA. Published online September 3, 2019. Full text, Editorial, Editorial

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