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Adjuvant endocrine therapy still misused, underused in patients with breast cancer
Use of adjuvant endocrine therapy still varies widely and has not been optimal for women with breast cancer over the past decade, according to results of a retrospective cohort study.
“Endocrine therapy use has been steadily increasing, but optimal usage has not been achieved in the United States,” Dezheng Huo, MD, PhD, associate professor in the department of public health sciences at University of Chicago, told HemOnc Today. “Certain breast cancer patients are being deprived of this life-saving therapy.”
Approximately 15,000 lives may have been saved in the past 10 years if adjuvant endocrine therapy (AET) guidelines were followed by all patients, Huo said. Endocrine therapy has shown clinical benefit in preventing recurrence and mortality, but underreporting and misuse or underuse of treatment has been an existing issue.
Researchers used the National Cancer Data Base to identify 981,729 women (mean age, 60.8 years; standard deviation, 13.3 years) with stage I to III breast cancer treated between 2004 and 2013 to determine specific temporal trends and factors related to receiving AET for breast cancer. Among the patients, 818,435 had hormone receptor–positive cancer and 163,294 had hormone receptor–negative cancer.
“AET misuse here indicates that patients with estrogen receptor–negative cancer received AET, which is not necessary,” Huo said. “Underuse of AET means that patients with estrogen receptor–positive disease did not receive AET.”
The number of patients with hormone receptor–positive cancer who received AET increased from 69.8% in 2004 to 82.4% in 2013, which represented an annual percentage change of 1.51% (95% CI, 1.48-1.54). The number of patients with hormone receptor–negative cancer who received AET decreased from 5.2% in 2004 to 3.4% in 2013, an annual percentage change of –0.17% (95% CI, –0.14 to –0.21)
Hospital-level adherence — defined as more than 80% of patients with hormone receptor–positive cancer receiving AET — increased from 40.2% in 2004 to 69.2% in 2013.
Whether a patient with hormone receptor–positive disease received AET varied based on age, race, geographic location and hormone receptor status. The rate was highest among women aged 50 to 69 years (> 80%) but low among patients aged 80 years and older (60.5%). A greater proportion of non-Hispanic white patients received AET (79%) compared with black (76.4%) and Hispanic patients (75.9%).
Use of AET was highest in New England (83.3%) and West North Central states (83.9%) but lowest in West South Central states (71.2%).
Further, only 51.2% of patients with ER–negative, PR–positive disease received AET.
The time to initiation of AET was more influenced by whether radiotherapy or chemotherapy were given than on surgery type. Median duration from diagnosis to AET was 75 days for patients who did not receive radiotherapy or chemotherapy, compared with 112 days for patients who received radiotherapy alone, 202 days for patients who received chemotherapy alone and 241 days for patients who received both (P < .001).
Of 174,786 patients who did not initiate AET, 19.6% were recommended the therapy but refused it, 4.6% were recommended therapy but were not given it without a reason, and 5.4% were not recommended for it based on certain risk factors.
Among HR–negative patients — 4.2% of whom inappropriately received AET — misuse of AET was more common among patients treated in low-volume hospitals (4.6%) and patients living in West South Central states (5.4%).
During a median follow-up of 4.9 years, 76,565 patients died. Adjusted multivariable Cox proportional hazards models showed the receipt of AET was associated with a 29% relative risk reduction in mortality (HR = 0.71; 95% CI, 0.7-0.73). Based on these data, researchers calculated that 14,630 lives would have been saved if AET was given according to guidelines for all women with hormone receptor–positive disease.
The researchers noted that AET is known to be underreported in registry data, which also lacks information on family history and genomic profile.
“More measures should be taken to further improve the use of AET in women who are supposed to receive the life-saving treatment,” Huo said. “Team-based oncological care may improve compliance to guidelines. Effective communication and education on the benefit of AET may also be important.” – by Melinda Stevens
For more information:
Dezheng Huo , MD, PhD, can be reached at Department of Public Health Sciences, University of Chicago, 5841 S Maryland Avenue, MC 2000, Chicago, IL; email: dhuo@health.bsd.uchicago.edu.
Disclosure : Huo reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Perspective
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The study by Daly and colleagues is an excellent example of a high-quality study that tells an important story, and teaches us several valuable lessons. I commend the researchers for their work.
First, this retrospective analysis of the National Cancer Data Base reminds us of the power of adjuvant endocrine therapy for reducing breast cancer mortality. We know from previously published meta-analyses that 5 years of tamoxifen in adjuvant trials reduced breast cancer mortality by approximately 33%. In a remarkable show of consistency, the study by Daly and colleagues showed that receipt of adjuvant endocrine therapy in women — in a nonclinical trial setting — with stage I to stage III hormone receptor–positive breast cancer was associated with a 29% relative risk reduction in mortality. This is precisely why receipt of adjuvant endocrine therapy in patients with ER–positive breast cancer has been endorsed as a national performance-based quality measure by the National Quality Forum and CMS.
Second, this study illustrates the problem of unexplained clinical variation, and why it is a major obstacle to high-quality health care. The researchers determined receipt of adjuvant endocrine therapy varied significantly by age, type of local treatment received, geographic region, and race and ethnicity. It is particularly alarming to see such great variation on a national level for a rather simple medical invention such as receipt of adjuvant endocrine therapy.
The researchers in this study attempted to identify why patients had not received adjuvant endocrine therapy. In only 25% of cases were they able to identify that adjuvant endocrine therapy was recommended but refused by the patient, or not recommended due to medical comorbidities. There was no available explanation for the remainder of cases.
Disparities in breast cancer outcomes between white and black or Hispanic women is not new in the literature. However, these results rather clearly indicate that survival disparities in women with hormone receptor–positive breast cancer could be readily addressed by working toward improving receipt of adjuvant endocrine therapy. This ties in nicely with another study of Medicare part D enrollees, results of which suggested that disparities in persistence of adjuvant endocrine therapy between white, black and Hispanic women are driven primarily by economic considerations. The researchers found a much higher rate of discontinuation of adjuvant endocrine therapy after just 1 year among black and Hispanic women without a prescription subsidy. Conversely, these disparities were almost entirely reversed among patients who had received assistance with out-of-pocket medication costs.
Finally, this study conveys a message of optimism. Progress in adjuvant endocrine therapy use has been made over the past decade. Among patients with hormone receptor–positive disease, receipt of adjuvant endocrine therapy improved from 70% in 2004 to 82% in 2013. Daly and colleagues showed improvements in hospital-level adherence, defined as more than 80% of patients with hormone receptor–positive disease receiving adjuvant endocrine therapy. In 2004, only 40% of hospitals included in the study were adherent. By 2013, this rate increased to 69%.
I am hopeful that collection of adjuvant endocrine therapy adherence as a national quality metric will help drive improved adherence — thus reducing clinical variation — and saving more women’s lives from breast cancer regardless of race or geography.
Biggers A, et al. J Clin Oncol. 2016;34:4398-4404.