College of American Pathologists

  Special Edition Issue


New CAP/ASCO Recommendations for ER/PgR and HER2 Testing in Breast Cancer

Posted March 16, 2011

Julie Katz Karp, MD

Breast cancer is the most common cancer in American women, with more than 200,000 new cases diagnosed in 2010. A breast cancer diagnosis typically requires radiologic imaging followed by tissue sampling to determine the histologic type and grade of the malignancy. Following a diagnosis of invasive carcinoma, immunohistochemical staining of the tissue specimen allows the pathologist to provide additional prognostic and predictive information, specifically regarding the expression of estrogen (ER) and progesterone (PgR) receptors and human epidermal growth factor 2 (HER2).

ER and PgR testing determines the likelihood of patient response to endocrine therapies. Multiple studies describe various measures of survival all with positive correlations to ER and PgR levels. HER2 overexpression is associated with worse prognosis in patients not receiving adjuvant therapies, and HER2 status can be used to predict patient sensitivity or resistance to various systemic therapies. These markers are now integral to clinical decisions regarding breast cancer treatment.

Tissue fixation in neutral buffered formalin alters protein antigen expression, and spurious immunohistochemical results can be seen in specimens fixed for abbreviated or prolonged intervals. In recent years, it was noted that the length of time between breast tissue acquisition and placement in fixative, as well as the length of time in fixative, influences the results of ER, PgR, and HER2 testing. In response to these findings, the College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO) provided guidelines for HER2 testing (2007) and ER and PgR testing (2010). The 2010 guidelines reflect more recent research and, as such, the two sets of guidelines have been reconciled to allow for uniform handling of breast cancer specimens. These guidelines were created to help standardize laboratory testing and ensure more accurate results for patients.

The reconciled guidelines make several recommendations that are particularly relevant to clinicians. The time between breast tissue removal and the initiation of fixation should be documented to be less than or equal to one hour. Additionally, breast tissue resection specimens that are not immediately examined, such as those acquired in a location remote from the pathology laboratory, should be bisected through the tumor upon removal to improve fixation. Documentation of the time of removal, fixative type, and time of fixation is also recommended. Specimens for ER and PgR levels should have six to 72 hours of formalin fixation, while those for HER2 testing should be fixed for six to 48 hours.

Core needle biopsies are often preferred for predictive factor testing because complete penetration of the specimen by formalin occurs more rapidly and fixation, therefore, tends to be more consistent. Resection specimens were initially preferred for HER2 testing because of greater heterogeneity of staining compared with hormone receptors and because of possible “edge artifact” in core needle biopsies causing false positive results. However, accurate testing can be achieved using either core needle biopsies or resection specimens. Pathologists should use discretion in selecting tissue samples for testing. Research in breast cancer treatment is ongoing, and our understanding of hormone receptors, gene overexpression, and clinical response to cancer treatment will develop over time. Guidelines will change in the future as the literature evolves. The above guidelines serve to standardize and maximize our current knowledge and provide the best possible care for breast cancer patients.

References and Suggested Reading

  1. Cancer and Women. Centers for Disease Control and Prevention website. Updated May 3, 2010. Accessed February 22, 2011.
  2. Breast Cancer. US National Institutes of Health National Cancer Institute website. Updated Accessed February 22, 2011.
  3. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18–43.
  4. Hammond ME, Hayes DF, Dowsett, M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010;134:907–922.

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NewsPath® Editor: C. Leilani Valdes, MD
This newsletter is produced in cooperation with the College of American Pathologists Public Affairs Committee and the NewsPath Editorial Board and may be reproduced in whole or in part as a service to the medical community. Copyright © 2011 by the College of American Pathologists.
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