Appropriate use of adjuvant endocrine therapy for breast cancer improved over a 10-year period, but optimal use has not been achieved, according to findings from a retrospective review of more than 980,000 women with stages I-III breast cancer.

As a result, an estimated 14,630 lives were unnecessarily lost during the study period, according to Bobby M. Daly, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Of the 981,729 women in the National Cancer Database from Jan. 1, 2004, to Dec. 31, 2013, who received all or part of their care at the reporting institution and who met eligibility criteria, 818,435 had hormone receptor positive (HR+) disease and 163,294 had hormone receptor negative (HR-) disease.

The percentage of HR+ patients receiving adjuvant endocrine therapy (AET) increased from 69.8% in 2004 to 82.4% in 2013 (annual percentage change, 1.51%), and the percentage of HR- patients decreased from 5.2% to 3.4% during the same time period (annual percentage change, -0.17%), the authors reported online Feb. 2 in JAMA Oncology (2017 Feb 2. doi: 10.1001jamaoncol.2016.6380 ).

Hospital level adherence, defined as meeting the 80% threshold of guideline concordant care, improved from 40.2% to 69.2% during the study period, they found.

Notably, receipt of AET varied significantly by age, race, geographic location, and receptor status. For example, more than 80% of those aged 50-69 years received AET, compared with 79.1% of those younger than age 40 years and 60.5% of those 80 years or older. African American and Hispanic patients were less likely than non-Hispanic white patients to receive AET (76.4% and 75.9% vs. 79.0%, respectively). The latter finding could be an important contributing factor to the racial disparity in breast cancer survival, the authors noted.

Facility factors also played a role in AET receipt; the rate of receipt varied substantially by facility volume and geographic location.

“We found that facilities in west south central states and low-volume institutions were more likely to misuse and underuse AET,” the investigators wrote, noting that these deficits could affect breast cancer mortality, as geographic differences in such mortality are well documented.

AET receipt also varied based on hormone receptor status, tumor size, and local treatment. Surgery and radiotherapy were the factors most significantly associated with appropriate AET receipt, with only 45% of those who underwent lumpectomy without radiotherapy receiving AET, compared with 90.1% of those receiving postmastectomy radiotherapy, 85.5% in those with postlumpectomy radiotherapy, and 73.2% of those with mastectomy alone.

Women included in this study were age 18 years or older (mean age, 60.8 years). Those undergoing surgery but receiving no neoadjuvant systemic treatment were eligible. Those with prior cancer diagnoses or with missing hormone receptor or AET status were excluded.

Based on recent trial results, the American Society of Clinical Oncology updated treatment guidelines in 2016 to recommend ovarian suppression for 5 years in combination with AET for high-risk premenopausal women, and AET alone both for women with stage I breast cancers that don’t warrant chemotherapy and for node-negative cancers of 1.0 cm or less.

“Similarly, the National Quality Forum (cancer measure 0220) endorsed tamoxifen or a third-generation aromatase inhibitor (considered or administered) within 1 year of diagnosis as a marker of quality care for patients with HR+ American Joint Committee on Cancer stage T1cN0M0, II, or III disease,” the researchers wrote. Studies demonstrated benefit with AET even in those with node-negative cancers of 1.0 cm or less, they added.

Improving adherence to these guidelines has lifesaving potential. In the current cohort, receipt of AET was associated with a 29% relative risk reduction in mortality, after adjusting for numerous patient, disease, and facility-related factors. This suggests that if all women with HR+ disease received AET in concordance with guidelines, 14,630 more lives would have been saved over the 10-year study period, the investigators said.

As for approaches that could help improve the appropriate use of AET, the findings of this cohort study support those from previous studies suggesting that a team-based approach is of benefit.

The finding that local treatments are key factors associated with appropriate AET use suggests that patients who undergo radiotherapy may be more likely to receive standard-of-care therapy in general, the authors explained, adding that “with more physicians involved in a patient’s care, these patients would be more likely to be recommended for guideline concordant care.

“Facilitation of multidisciplinary team-based care may help optimize guideline-concordant treatment by ensuring patients are not lost to follow-up and are recommended for evidence-based care,” the study authors concluded.

Their hope is that with the coming launch of the Medicare Access and Chip Reauthorization Act and value-based reimbursement, efforts will be made to close the quality gap affecting patients in certain age groups, racial minority groups, and geographic regions, and to thereby prevent the loss of lives.

MACRA may boost outcomes

In an interview, Dr. Daly said he believes the coming changes with respect to value-based reimbursement will indeed have an important impact on outcomes.

“The oncology care model, for example, mandates that physicians document that they are providing guideline-concordant care,” said Dr. Daly, assistant attending physician at Memorial Sloan Kettering Cancer Center. “There are also new technologies such as oncology clinical pathways … that also try to ensure that all patients are receiving care according to guidelines.”

Further, the increasing use of team-based approaches to care and the incorporation of “tumor boards” might explain the growth in optimal AET usage seen in this cohort.

Dr. Daly said he was surprised to find that certain patient groups were being left behind, such as those with estrogen receptor-negative/progesterone receptor-positive disease, African American patients, and younger and older patients, who were less likely to receive AET.

“I think that helps us also focus on patient populations we can target to make sure they are receiving optimal care,” he said, stressing that the findings have important policy implications for figuring out why those patients are being left behind, and raising the standard of care for all patients.

“We are making great strides to providing appropriate guideline-concordant care for breast cancer patients, but there’s still room to improve,” he said.

Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.


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