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Honing Chemo Use in Small Breast Tumors

— Clearest survival benefit for 8-10 mm tumors in HR/HER2-positive disease

Last Updated May 5, 2020
MedpageToday
A woman reads a magazine while receiving chemotherapy

Among women with small node-negative, hormone receptor (HR)-positive, HER2-positive breast cancers, tumors 8-10 mm appeared to derive the most benefit from chemotherapy, a review of a large national database suggested.

Chemotherapy, in addition to hormonal therapy, was associated with a 47% reduction in the survival hazard for women with tumors 8-10 mm, but did not offer a survival benefit to women with smaller tumors. Similar findings came from a matched-pair analysis.

The findings added more information to the clinical decision-making process regarding the need for chemotherapy to treat small HR-positive/HER2-positive breast cancers, Anurag K. Singh, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, and co-authors reported in .

"It wasn't clear what to do with these patients, who make up a really small population of breast cancer patients," Singh told ֱ. "We know that if you have an ERBB2 [HER2] tumor, it's worse, and the idea has been they should get chemotherapy."

"You have an otherwise healthy, 60-year-old, mammographically screened and detected patient," Singh continued. "When you give them the information, they're saying, 'OK, I have all of these good things, but I've got a 2-mm tumor and you want to give me 6 months of chemo. Are you serious? I'm going to lose my hair, I'm going to have this, I'm going to have that. It seems like an awful long way to go.' We didn't really have good evidence for them."

Women with small (≤10 mm) node-negative, HR-positive/HER2-positive breast tumors make up a heterogeneous population, with 5-year recurrence rates ranging from 5-25% with or without adjuvant therapy, the authors noted in their introduction. The current acknowledges the lack of representation of such patients in clinical trials and recommends consideration of chemotherapy for tumors ≤10 mm at the treating physicians' discretion.

In the absence of randomized trial data to inform decision making, the cutoff for tumor size indicating when chemotherapy can be omitted remains unclear, they continued. To address the uncertainty, investigators queried the U.S. to identify women with HR-positive/HER2-positive breast cancers (pT1a-bN0) that were diagnosed from 2010 to 2015 and who received hormonal therapy with or without chemotherapy. The primary objective was overall survival (OS).

Data analysis included 10,065 patients who had a median age of 59 and a median follow-up of 41.8 months. The total comprised 5,346 women who received chemotherapy and 4,719 who did not. By multivariable analysis, chemotherapy was associated with a 31% reduction in the survival hazard ratio (95% CI 0.52-0.90, P=0.006). Analysis of tumor size as a continuous variable showed a 7% increase in mortality with each 1-mm increase (95% CI 1.03-1.12, P=0.002).

Investigators found a statistically significant interaction between multiagent chemotherapy and tumor size (P=0.02). A multivariable analysis of tumor size ranging from 2-9 mm showed that an 8-mm cutoff achieved statistical significance (P for interaction = 0.01). Multiagent chemotherapy did not improve OS for patients with tumors smaller than 8 mm (HR 1.00, 95% CI 0.70-1.43). In contrast, an analysis of tumors 8-10 mm favored use of chemotherapy (HR 0.53, 95% CI 0.36-0.78).

Finally, investigators performed a matched-pair analysis of 1,641 patients with tumors <8 mm in size and 648 patients with tumors 8-10 mm. Again, chemotherapy did not improve OS in patients with tumors <8 mm (HR 0.88, 95% CI 0.58-1.34), but reduced the hazard by 52% in patients who had tumors 8-10 mm (95% CI 0.27-0.85).

Singh intends to use the data in patient discussions about treatment options, keeping in mind the heterogeneous nature of the population of patients with these types of small tumors.

"This makes the conversation with patients easier," he said. "If a patient has a 2-mm tumor I can say, 'I really don't want to offer you chemotherapy.' But there will also be patients with 1-mm tumors who say, 'My mom and my grandmother died of breast cancer, and I absolutely want to get chemotherapy.'"

As a final consideration, Singh noted that although patients with small HR-positive/HER2-positive breast cancers represent a small segment of the overall patient population, because breast cancer is so prevalent, the cumulative impact is much greater -- 10,000 patients over 5 years in this study.

  • author['full_name']

    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined ֱ in 2007.

Disclosures

Singh reported having no relevant relationships with industry.

Primary Source

JAMA Network Open

Ma SJ, et al "Association of survival with chemoendocrine therapy in women with small, hormone receptor-positive, ERBB2-positive, node-negative breast cancer" JAMA Netw Open 2020; DOI: 10.1001/jamanetworkopen.2020.2507.