Should Low Estrogen Receptor Status Be Considered Positive?

Breast Cancer News
May 30, 2014
Robin Warshaw, Contributing Writer
Reviewed By: 
Virginia Kaklamani, MD, DSc

Breast cancers with a low level of estrogen receptor positivity – only 1 to 9 percent of tumor cells being positive – is more similar to ER-negative disease than to breast cancer with ER positivity of 10 percent or greater, according to a recent study.

The researchers noted that although hormonal (endocrine) therapy is very helpful in ER-positive disease, among people taking hormonal therapy, those with weak ER positivity had worse overall survival, recurrence-free survival and distant recurrence-free survival than did those in the higher ER-positive group.

Background and Reason for the Study

Breast cancer cells may have estrogen receptors, proteins that cause growth by receiving signals from estrogen in the bloodstream. When these hormone receptors are present, the cancer is called estrogen receptor-positive, or ER-positive.

ER-positive breast cancers usually respond well to hormonal therapies, such as tamoxifen or aromatase inhibitors, which block growth signals. Yet the strength of ER positivity, measured by percentage of estrogen receptors in breast cancer cells, varies from cancer to cancer and may affect how well hormonal therapy works.

There has been little data showing what percent of positive cells must exist for a cancer to qualify as ER-positive. Many doctors have used 10 percent or greater as that threshold, but some have used lower or higher percentages as well. Guidelines from the American Society of Clinical Oncology and the College of American Pathologists recommend a threshold of 1 percent or more for demonstrating that breast cancer is ER-positive.

The researchers of this study wanted to find out if a defined point for ER positivity could be determined.

Study Structure

Using a large cancer center database, the researchers examined records for people with early-stage breast cancer and grouped them by the cancer’s known ER status:

  • ER-positive, 10 percent or greater positive cells (high positivity)
  • ER-positive, 1 – 9 percent positive cells (low positivity)
  • ER-negative

Researchers then analyzed personal and tumor characteristics and treatments and outcomes, by comparing results between those groups.


The study included 9,639 people. The ER status of their cancer divided them into three groups:

  • 80.5 percent high positivity
  • 2.6 percent low positivity
  • 16.9 percent ER-negative

On average, the high ER-positive group was older (median age, 56) than the low ER-positive (median age, 53) or ER-negative (median age, 52) groups.

Compared with high positivity participants, those with low positivity were less likely to be white or receive hormonal therapy and more likely to

  • have stage II or III disease.
  • have HER2-positive cancer.
  • receive adjuvant (after surgery) chemotherapy.
  • have cancer only in the breast and nearby lymph nodes.

In people who received hormonal therapy, those with low positivity had higher rates of breast cancer returning, called recurrence, than did those with high positivity. No significant difference in recurrences was found between the low ER-positive and ER-negative groups.

The researchers concluded that low ER-positive breast cancer was more similar to ER-negative disease than it was to high ER-positive. Hormonal therapy did not seem to benefit low ER-positive cancers.

It was recommended that future studies focus on the low ER-positive cancers.

Study Limitations

The study was retrospective, meaning it looked back at data collected a long time ago, and did not randomly assign treatment. Randomly assigning treatment helps researchers collect the best possible data on how well treatments work in different people.

Another hormone receptor, the progesterone receptor (PR), also may provide added information on the benefit of hormonal therapy in women diagnosed with breast cancer, but was not assessed in this study.

What This Means for You

Only a small portion of ER-positive breast cancers fall into the low positivity group. Your pathology report should tell you if the cancer is ER-positive. Talk with your doctor to understand whether the cancer has high or low positivity, and how that might affect your treatment plan.

Physicians may use this study to counsel those diagnosed with breast cancer on the potential benefit of hormonal therapy.

The LBBC Guide for the Newly Diagnosed can help you understand more about the biology of breast cancer, your diagnosis and questions you may want to ask your healthcare providers.

Yi, M, Huo, L, Koenig, KB et al. Which Threshold for ER Positivity? A Retrospective Study Based on 9,639 PatientsAnnals of Oncology. 2014; doi: 10.1093/annonc/mdu05

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Additional Related Topics 
Hormonal Therapy