Breast

Contributed by Anand C. Annan, M.D., Ph.D., Doaa Atwi, M.D. and Lewis A. Hassell, M.D.

Contributed by Terry Dunn, Ph.D.

• Breast, left, ultrasound guided core needle biopsy:
  • Invasive breast carcinoma of no special type (ductal), grade 2
    • Estrogen receptor: positive (90%, strong intensity)
    • Progesterone receptor: positive (70%, intermediate intensity)
    • HER2 by IHC: negative (score 1+) (see comment)
  • Comment: Patients with breast cancers that are HER2 IHC 3+ or IHC 2+ / ISH amplified may be eligible for several therapies that disrupt HER2 signaling pathways. Invasive breast cancers that test HER2 negative (IHC 0, 1+ or 2+ / ISH not amplified) are more specifically considered HER2 negative for protein overexpression / gene amplification despite having some level of protein expression. Patients with breast cancers that are HER2 IHC 1+ or IHC 2+ / ISH not amplified may be eligible for treatment with a cytotoxic drug regimen that targets nonamplified / nonoverexpressed levels of HER2 (IHC 0 results do not currently result in eligibility).

According to the current 2023 update of American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines for HER2 interpretation in breast cancer, how should the IHC result (see image above) be interpreted in a pathology report?

1. HER2 negative (score 0)
2. HER2 negative (score 1+)
3. HER2 low positive (score 1+)
4. HER2 positive (score 3+)

B. HER2 negative (score 1+). The above IHC for HER2 shows faint / incomplete staining for HER2 in > 10% of tumor cells and is therefore interpreted with a score of 1+. Answer D is incorrect because as per the 2023 ASCO / CAP update, this IHC result should still be HER2 negative. Answer A is incorrect because tumors demonstrating HER2 IHC score 0 expression show no staining or ≤ 10% incomplete, faint / barely perceptible staining. Answer C is incorrect because although this is considered HER2 low positive, ASCO / CAP guidelines do not recommend using this terminology in the pathology report at this time. See 2023 ASCO / CAP update on HER2 interpretation (J Clin Oncol 2023;41:3867).

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Reference: HER2 low breast cancer

What is the current understanding of the prognostic implication of HER2 low positive breast cancer patients?

1. HER2 low breast cancer patients with an IHC score of 2+ have a better prognosis that those with an IHC score of 1+
2. There is no definite evidence of distinct prognostic implications
3. They have a better prognosis than HER2 negative (score 0) patients
4. They have a poorer prognosis than HER2 negative (score 0) patients

B. There is no definite evidence of distinct prognostic implications. Answers A, C and D are incorrect because although there is some evidence in the literature that shows poorer prognoses for HER2 low patients compared to HER2 negative (score 0) patients, there is no distinct prognostic or predictive implications for HER2 low status.

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Reference: HER2 low breast cancer