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Chemotherapy for Certain Small, Hormone-Receptor-Positive, HER2-Positive Breast Cancers Seems to Improve Survival

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When looking at treatment outcomes for small, hormone-receptor-positive, HER2-positive breast cancers that have not spread to the lymph nodes, a study suggests that women diagnosed with cancers 8–10 mm (about 0.31 inches to 0.39 inches) in size had better survival when they were treated with chemotherapy after surgery compared to women diagnosed with smaller cancers.

The research was published on April 9, 2020, by the journal JAMA Network Open. Read the abstract of “Association of Survival With Chemoendocrine Therapy in Women With Small, Hormone Receptor-Positive, ERBB2-Positive, Node-Negative Breast Cancer.”

The HER2 gene is also called the ERBB2 (Erb-B2 receptor tyrosine kinase 2) gene.

Why the study was done

Research shows that very small, node-negative, hormone-receptor-positive, HER2-positive breast cancers have a 5-year recurrence risk — the risk of the cancer coming back within 5 years — that ranges from 5% to 25%, with or without treatments after surgery. Doctors call treatments given after surgery adjuvant treatments.

Because HER2-positive cancer is considered more aggressive than HER2-negative breast cancer, it is usually treated with chemotherapy after surgery to reduce recurrence risk. Still, it has been unclear whether the benefits of treating very small, node-negative, hormone-receptor-positive, HER2-positive breast cancers with chemotherapy after surgery outweighed the risks.

“It wasn’t clear what to do with these patients, who make up a really small population of breast cancer patients,” Anurag Singh, M.D., of Roswell Park Comprehensive Cancer Center, one of the researchers who did the study, said in an interview.

“We know that if you have an ERBB2 tumor, it's worse, and the idea has been they should get chemotherapy,” he continued. “You have an otherwise healthy 60-year-old, mammographically screened and detected patient. 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.”

How the study was done

The researchers looked at the records of 10,065 women diagnosed with node-negative, hormone-receptor-positive, HER2-positive breast cancer that was 10 mm or smaller in size between 2010 and 2015.

All of the women were treated with hormonal therapy after surgery:

  • 5,346 women also were treated with chemotherapy after surgery
  • 4,719 women were not treated with chemotherapy

From 2013 to 2015, anti-HER2 therapy such as Herceptin (chemical name: trastuzumab) was coded differently than chemotherapy in patient records; 15% of the women treated during this time had either chemotherapy or anti-HER2 therapy alone.

Follow-up time ranged from about 2 years to about 5 years.

The researchers compared the outcomes of women treated with hormonal therapy and chemotherapy to women treated with hormonal therapy alone. They also looked to see if the size of the cancer affected any benefits from chemotherapy.

The analysis showed that chemotherapy was associated with better overall survival for women diagnosed with cancers that were 8–10 mm in size. Women diagnosed with cancers that were smaller did not seem to get any survival benefits from chemotherapy.

“To our knowledge, this is the first report to suggest that there is an association between improved survival and adjuvant chemoendocrine therapy specifically for HR-positive, ERBB2-positive tumors 8 mm to 10 mm compared with those smaller than 8 mm,” the researchers wrote. “It is evident that tumors 10 mm and smaller represent a heterogeneous group whose treatment should be tailored to improve the risk-to-benefit ratio of systemic therapy.”

What this means for you

The results of this study offer helpful information about which women may benefit from chemotherapy after surgery for very small, hormone-receptor-positive, HER2-positive breast cancer that hasn’t spread to the lymph nodes.

Still, the results are based on extremely small differences in cancer size — millimeters — and require expert pathology review of the cancer. The researchers also didn’t know the exact chemotherapy regimens the women had.

Also, anti-HER2 medicines, such as Herceptin, are often given along with chemotherapy. In this study, for 2 years of the 5-year study, anti-HER2 therapy and chemotherapy were not coded differently. So, a number of women may have been receiving both anti-HER2 therapy and chemotherapy during that time, which may have affected the study results.

If you’ve been diagnosed with a very small, hormone-receptor-positive, HER2-positive breast cancer that hasn’t spread to the lymph nodes and are considering treatments after surgery, it makes sense to talk about this study with your doctor. The results offer more information about outcomes and can help you decide on the best treatments for your unique situation.

For more information on chemotherapy, including types of medicines and side effects, visit the Breastcancer.org Chemotherapy pages.

Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser


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