Neoadjuvant Endocrine Therapy Underused for Breast Cancer

Kate O'Rourke

March 04, 2016

BOSTON — Roughly 5 years ago, a study demonstrated that neoadjuvant endocrine therapy increases the rates of breast conservation surgery in patients with breast cancer as a result of the downstaging of disease.

Now, an analysis of roughly 80,000 women with breast cancer in the United States shows that this study has done little to increase the use of this treatment modality.

"Neoadjuvant endocrine therapy use has increased since the publication of Z1031 [the American College of Surgeons Oncology Group (ACOSOG) Z1031 study]. However, the overall rate of neoadjuvant endocrine therapy use is low, at 3.2%," said Akiko Chiba, MD, a breast surgery fellow at the Mayo Clinic, Rochester, Minnesota, who presented the study at the Society of Surgical Oncology (SSO) 2016 Cancer Symposium.

Dr Chiba and coinvestigators identified a small but statistically significant increase in the use of neoadjuvant endocrine therapy, from 2.6% before and during Z1031 to 3.2% after Z1031 (P < .001), a period from 2004 to 2012.

The study seemed to demonstrate an immediate effect, but in absolute terms, it is a small increase.

"Surgeons should consider the use of neoadjuvant endocrine therapy in patients with hormone receptor–positive breast cancer who are interested in breast conservation," said Dr Chiba.

Neoadjuvant systemic therapy is not a foreign idea.

Neoadjuvant chemotherapy is widely accepted for use in biologically aggressive breast cancer, such as triple-negative and HER2-positive tumors. It is known to lead to the downstaging of disease in the breast and axilla and to increase rates of breast conservation surgery.

However, it is a different story for hormone receptor-positive disease, said Dr Chiba. She explained that, in these patients, response rates to neoadjuvant chemotherapy are low, and most of the systemic benefit is from endocrine therapy.

"Delivery of endocrine therapy in the neoadjuvant setting can also downstage disease in the breast and increase breast-conserving surgery rates," she emphasized.

In 2010, this was demonstrated in the Z1031 study. At that time, researchers from this study reported that neoadjuvant endocrine therapy increases the rate of breast conservation surgery for postmenopausal women with clinical tumor stage 2-4c estrogen receptor (ER)–positive and progesterone receptor (PR)–positive breast cancer (J Clin Oncol. 2011;29:2342-2349).

Of 163 patients in Z1031 who were thought to require mastectomy at the initial presentation, 51% underwent breast conservation surgery after endocrine therapy and were successfully treated. "While neoadjuvant endocrine therapy is commonly used in Europe, it's infrequently used in the United States," said Dr Chiba.

It's infrequently used in the United States. Dr Akiko Chiba

Some Reasons for the Underutilization

In the study presented here at the SSO meeting, Dr Chiba and colleagues set out to determine whether ACOSOG Z1031 has had an impact on practice.

Investigators identified all cT2-4c ER- and PR+ breast cancer patients aged 50 years or older in the National Cancer Data Base from 2004 to 2012. They excluded patients who received neoadjuvant chemotherapy and/or radiation therapy. The researchers analyzed the use of neoadjuvant endocrine therapy during three periods, pre-Z1031 (2004-2006), during Z1031 (2007-2009), and post-Z1031 (2010-2012).

Of the 79,909 patients identified, 86% had clinical stage T2 tumor, 10% had clinical stage T3 tumor, and 4% had clinical stage T4a-c tumor.

In cT2 patients, use of endocrine therapy increased from 1.8% pre-Z1031 to 2.4% post-Z1031 (P < .001). In cT3 patients, use was 5.9% pre-Z1031 and 7.1% in the post-Z1031 period (P < .001). The highest use of endocrine therapy occurred in patients with clinical stage T4 tumor, but the increase over time was not statistically significant (8.9 vs 11.0%; P = .19).

The increased use of endocrine therapy translated into an increase in the number of patients undergoing breast-conserving surgery in comparison with the number of patients who did not receive endocrine therapy (46.3% vs 43.8%, P=.02). This was true for all clinical stages: cT2 (58.7% vs 47.9%; P = .02), cT3 (25.8% vs 14.9%; P < .001), and cT4a-c (24.6% vs 20.0%; P = .04). "One in four women with clinical tumor stage T3 and T4 were able to undergo breast conservation after neoadjuvant endocrine therapy," said Dr Chiba. The use of endocrine therapy was highest in the Northeast and lowest in the Intermountain West.

"I don't think neoadjuvant endocrine therapy has taken traction like neoadjuvant chemotherapy has, but I think a study like this can point out some of the benefits," said Julie Margenthaler, MD, a breast cancer surgeon at Barnes-Jewish Hospital, in St. Louis, Missouri, who was not involved with the study. "Probably the biggest one is to convert patients from more extensive surgery to less extensive surgery and potentially do breast-conserving therapy in a larger percentage of people."

She characterized neoadjuvant endocrine therapy as very underutilized. "I think that one of the reasons it has been underutilized is that you don't see those dramatic complete responses that you see with chemotherapy and targeted therapy, because it takes a long time," said Dr Margenthaler. "It is 4 months of treatment, and it is a less robust result at the end." She says clinicians at her institution often use neoadjuvant endocrine therapy.

Dr Chiba and Dr Margenthaler have disclosed no relevant financial relationships.

Society of Surgical Oncology (SSO) 2016 Cancer Symposium: Abstract 19. Presented March 3, 2016.


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