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Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer

Modern Pathology volume 34, pages 875–882 (2021)Cite this article

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Abstract

Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) who do not experience a pathologic complete response (pCR), the pattern of residual disease in the breast varies. Pre-treatment clinico-pathologic features that predict the pattern of residual tumor are not well established. To investigate this issue, we performed a detailed review of histologic sections of the post-treatment surgical specimens for 665 patients with stage I-III breast cancer treated with NAC followed by surgery from 2004 to 2014 and for whom slides of the post-NAC surgical specimen were available for review. This included 242 (36.4%) patients with hormone receptor (HR)+/HER2− cancers, 216 (32.5%) with HER2+ tumors, and 207 (31.1%) with triple negative breast cancer (TNBC). Slide review was blinded to pre-treatment clinico-pathologic features. pCR was achieved in 7.9%, 37.0%, and 37.7%, of HR+/HER2− cancers, HER2+ cancers, and TNBC respectively (p < 0.001). Among 389 patients with residual invasive cancer in whom the pattern of residual disease could be assessed, 287 (73.8%) had a scattered pattern and 102 (26.2%) had a circumscribed pattern. In both univariate and multivariate analyses, there was a significant association between tumor subtype and pattern of response. Among patients with HR+/HER2− tumors, 89.4% had a scattered pattern and only 10.6% had a circumscribed pattern. In contrast, among those with TNBC 52.8% had a circumscribed pattern and 47.2% had a scattered pattern (p < 0.001). In addition to subtype, histologic grade and tumor size at presentation were also significantly related to the pattern of residual disease in multivariate analysis, with lower grade and larger size each associated with a scattered response pattern (p = 0.002 and p = 0.01, respectively). A better understanding of the relationship between pre-treatment clinico-pathologic features of the tumor and pattern of residual disease may be of value for helping to guide post-chemotherapy surgical management.

In current clinical practice almost all patients with invasive breast cancer receive some form of systemic therapy (i.e., chemotherapy, HER2-targeted therapy, endocrine therapy), the details of which depend upon the tumor subtype [1]. While this is often given after surgical removal of the tumor (i.e., in the adjuvant setting), systemic therapy after a core needle biopsy diagnosis of carcinoma but prior to definitive surgery (i.e, in the neoadjuvant setting) is being used increasingly, particularly for patients with triple negative and HER2-positive breast cancers [2, 3].

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Fig. 1: Schematic representation of patterns of residual disease following neoadjuvant chemotherapy.
Fig. 2: Histologic images of patterns of residual tumor.
Fig. 3: Treatment effects in invasive carcinoma cells.
Fig. 4: Tumor bed features related to tumor subtype.

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Author notes

  1. These authors contributed equally: Tari A. King, Stuart J. Schnitt

Affiliations

  1. Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA

    Ricardo G. Pastorello, Alison Laws, Samantha Grossmith, Claire King, Monica McGrath, Elizabeth A. Mittendorf & Tari A. King

  2. Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA

    Ricardo G. Pastorello, Alison Laws, Elizabeth A. Mittendorf, Tari A. King & Stuart J. Schnitt

  3. Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Stuart J. Schnitt

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  1. Ricardo G. Pastorello
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  2. Alison Laws
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  4. Claire King
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Correspondence to Stuart J. Schnitt.

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Pastorello, R.G., Laws, A., Grossmith, S. et al. Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer. Mod Pathol 34, 875–882 (2021). https://doi.org/10.1038/s41379-020-00714-5

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