Clinical Challenge: HER2-Positive Breast Cancer in Older Women

The median age at breast cancer diagnosis is 63, with about 20% of new cases occurring in women older than 75. HER2-positive breast cancer is less common in older women compared with younger women, but still occurs in about 10% to 15% of these patients, said Erin Roesch, MD, of Cleveland Clinic.

The use of HER2-targeted therapy may be underused in older women, specifically those with more locally advanced disease, Roesch noted. One study of more than 1,300 Medicare beneficiaries with stage I to III HER2-positive breast cancer showed that about half of patients age 65 or older did not receive trastuzumab-based therapy, and in fact, age older than 74 was found to be associated with a lower likelihood of receipt of this drug.

“It is noteworthy that this significant proportion of women with HER-positive breast cancer did not receive HER2-targeted therapy,” Roesch said.

Generally, older women are underrepresented in clinical trials of breast cancer, specifically trials examining HER2-targeted agents, said Hyman B. Muss, MD, of UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina.

Despite that, some combination of HER2-directed therapy with chemotherapy remains the accepted standard treatment for early and advanced HER2-positive breast cancer, regardless of a patient’s age. However, oncologists are in a unique position to do more for a patient than just assess her breast cancer, Muss emphasized.

“We have to remember that although the patient is in our office for breast cancer, that breast cancer may be just another bump on the road of life,” he said. “Maybe the patient has a lack of social support and has trouble getting meals, maybe she has fallen three times in the last year and needs balance support.”

This is where the use of geriatric assessments come in, Muss explained.

Assessing the Whole Patient

In 2018, the American Society of Clinical Oncology (ASCO) released a guideline recommending that anyone age 65 or older under consideration for chemotherapy undergo a geriatric assessment to identify vulnerabilities.

For clinicians in a busy practice, the G8 questionnaire or the Vulnerable Elders Survey (VES-13) could be completed at the beginning of an appointment or even over the phone when scheduling the appointment.

“Those in generally good health may not benefit from a formal assessment, which takes at least 20 to 30 minutes minimum,” Muss said. “There are new Medicare rules where we can bill based on time, but the problem is there often isn’t time.”

These assessments may be particularly important in women being assessed for HER2-directed therapy because of some of the associated side effects.

Studies that included older women treated with trastuzumab or other HER2-directed therapy have shown higher rates of congestive heart failure compared with those who did not receive these targeted agents, Roesch said. Additionally, women with existing cardiac comorbidities might be at higher risk.

“A cardiac risk assessment should be performed in older patients and referral to cardio-oncology as appropriate,” Roesch noted.

Muss said that he regularly performs baseline assessment of left ventricular ejection fraction with ultrasound.

“HER2-related cardiac toxicity is usually reversible, unlike that seen with an anthracycline,” Muss said. “It is important, though, that these patients are monitored at least every 3 months.”

Regimen Adjustments

Another consideration in older patients who may not have as much tolerance for treatment is adjustment of treatment duration. One year of adjuvant trastuzumab is the current standard of care, but some studies have explored other durations, like 6 months, Roesch explained.

“Results from these studies are not completely concordant,” she said. “Some have not been able to demonstrate that a shorter duration is noninferior to 1 year, while others have shown that 6 months is noninferior to 12 months, with less cardiotoxicity.”

Both Roesch and Muss agreed that a shorter duration may be an option in certain patients, such as those with lower-risk disease, node-negative tumors, or those with significant cardiac risk factors.

The recently published RESPECT study also showed that some women ages 70 to 80 may be able to skip chemotherapy and be treated only with trastuzumab. The primary endpoint of noninferiority was not met for trastuzumab monotherapy compared with trastuzumab chemotherapy, but researchers noted that “the observed loss of survival without chemotherapy was less than 1 month at 3 years.”

Muss also pointed to a study testing 12 weeks of adjuvant paclitaxel and trastuzumab plus 9 months of trastuzumab in women with small, node-negative, HER2-positive disease. The 3-year rate of invasive disease-free survival was 98.7%.

Other Considerations

In addition to the cardiac side effects of some HER2-directed therapies, Roesch pointed out that diarrhea, low platelet counts, and neuropathy can occur, all of which have to be carefully monitored in older patients.

“A lot of physicians might feel as though an ‘eyeball test’ is good enough to assess whether a patient is vulnerable, and it is not,” Muss said. “Older people frequently have a lot of comorbidities and other co-existing illness, polypharmacy, or social problems.”

If an oncologist is seeing two 30-year-old patients, it is unlikely that one will have dementia, but if they are seeing two 75-year-old patients, one might be a rock star physically and one might be bedfast and demented, he added.

“Oncologists are in a unique position to address these problems and improve the overall care of patients,” he continued. “The range of health in people in their 70s is vast and we have to get a handle on that before we can treat their cancer properly.”

Last Updated June 11, 2021