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Estrogen-Receptor-Negative, Progesterone-Receptor-Positive Breast Cancers: A Distinct Subtype?

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Breast cancers that are estrogen-receptor-negative and progesterone-receptor-positive should be considered a distinct breast cancer subtype, according to a study.

The research was published online on Jan. 3, 2020, by JAMA Network Open. Read “Clinicopathological Characteristics and Breast Cancer-Specific Survival of Patients With Single Hormone Receptor-Positive Breast Cancer.”

About hormone receptors and breast cancer

Hormone receptors are proteins found in and on the surface of breast cancer cells that pick up signals and tell the cells to grow.

A cancer is estrogen-receptor-positive if it has receptors for the hormone estrogen. A cancer is progesterone-receptor-positive if it has receptors for the hormone progesterone.

Breast cancers can be:

  • both estrogen-receptor-positive and progesterone-receptor-positive
  • both estrogen-receptor-negative and progesterone-receptor-negative
  • estrogen-receptor-positive and progesterone-receptor-negative
  • estrogen-receptor-negative and progesterone-receptor-positive

A breast cancer with either estrogen or progesterone receptors or both types of receptors is considered hormone-receptor-positive. Hormone-receptor-positive breast cancer treatment plans have certain standards of care, and these standards of care do not change if the breast cancer is positive for only one hormone receptor.

Because of the way the genes that make the estrogen receptor proteins and progesterone receptor proteins work, a number of doctors believe that it is biologically impossible for a breast cancer to be estrogen-receptor-negative and progesterone-receptor-positive.

So there has been controversy over whether estrogen-receptor-negative, progesterone-receptor-positive breast cancer is a true subtype or a misclassification made when less research had been done.

About this study

To do the study, the researchers analyzed information from 823,399 people diagnosed with breast cancer between 1990 and 2015 to see if there were differences in breast cancer-specific survival based on hormone-receptor status. The information came from the SEER databases, large registries of cancer cases from sources throughout the United States maintained by the National Institutes of Health.

Breast cancer-specific survival means whether or not a person died from breast cancer.

Of the 823,399 people, 818,002 were women and 5,397 were men. About half the people were older than 60 and half were younger. Half the people were followed for more than 71 months and half were followed for shorter periods of time.

  • 67.2% of the breast cancers were estrogen-receptor-positive and progesterone-receptor-positive
  • 19.0% of the breast cancers were estrogen-receptor-negative and progesterone-receptor-negative
  • 12.2% of the breast cancers were estrogen-receptor-positive and progesterone-receptor-negative
  • 1.6% of the breast cancers were estrogen-receptor-negative and progesterone-receptor-positive

The researchers found that breast cancer-specific survival differed based on hormone receptor status. These differences were statistically significant, which means that the differences were likely due to the difference in hormone receptor status and not just because of chance.

People diagnosed with breast cancer that was estrogen-receptor-positive and progesterone-receptor-positive had a 30% to 60% lower risk of dying from breast cancer compared to people diagnosed with breast cancer that was positive for only one hormone receptor.

For people diagnosed with breast cancer that was positive for only one hormone receptor, estrogen-receptor-positive breast cancer was linked to better breast cancer-specific survival compared to progesterone-receptor-positive breast cancer.

People diagnosed with breast cancer that was positive for one or both hormone receptors had better breast cancer-specific survival compared to people diagnosed with breast cancer that was negative for both hormone receptors.

“The results support the existence of the [estrogen-receptor]-negative/[progesterone-receptor]-positive subtype and indicate that [estrogen-receptor]-positive/[progesterone-receptor]-negative and [estrogen-receptor]-negative/[progesterone-receptor]-positive tumors are distinct subtypes of breast cancer,” the researchers concluded. “The assessment of [progesterone receptor] status provides valuable information for prognosis and for evaluating the benefit of endocrine therapy. Further studies and clinical trials are needed to optimize the treatment regimens for patients with single-hormone receptor-positive breast cancer.”

In an editorial that accompanied the study, Vasily Giannakeas, of the Women’s College Research, wrote, “It will remain a challenge to personalize treatment for [estrogen-receptor]-negative/[progesterone-receptor]-positive cancer considering that this subtype now constitutes only 1% of all breast cancers.”

What this means for you

This study offers more information about how hormone receptor status affects a breast cancer’s response to treatment and strongly suggests that breast cancer that is estrogen-receptor-negative and progesterone-receptor-positive should be a distinct subtype of breast cancer.

Still, more research is needed before we know the best way to treat estrogen-receptor-negative, progesterone-receptor-positive breast cancer. If you’ve been diagnosed with this rare subtype of breast cancer, it makes sense to talk to your doctor about this study and discuss the best treatment options for your unique situation.

For more information, visit the Breastcancer.org pages on Hormone Receptor Status.

Written by: Jamie DePolo, senior editor

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


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