Veerle Bossuyt, MD

Assistant Professor of Pathology

Research Interests

Breast; Breast Diseases; Breast Neoplasms; Genital Neoplasms, Female; Pathology; Precancerous Conditions; Carcinoma, Ductal, Breast; Breast Neoplasms, Male; Inflammatory Breast Neoplasms; Triple Negative Breast Neoplasms

Public Health Interests

Health promotion-disease prevention

Research Organizations

Pathology

Faculty Research

Yale Cancer Center

Office of Cooperative Research

Research Summary

My research activities focus on breast cancer. I work collaboratively with basic researchers, translational researchers and clinicians. My goal is to bring my knowledge of tumors and tissues derived from participating in clinical care to the multidisciplinary research team. My main area of expertise is in neoadjuvant breast cancer trials. I am a member of the BIG-NABCG residual disease characterization-working group; a member of the Working Group on Immuno-Oncology Biomarkers in Breast Cancer; and a member of the Pathology Committee, Translational Research Program, Alliance for Clinical Trials in Oncology (formerly ACOSAG, CALGB, NCCTG).

Extensive Research Description

One of my specific areas of expertise is in the evaluation of breast specimens after neoadjuvant therapy. The U.S. FDA put forward pathologic complete response (pCR) as an endpoint demonstrating treatment efficacy for (preliminary) regulatory approval of new agents for neoadjuvant treatment of high-risk early-stage breast cancer. However there is a great variety in approaches to pathologic evaluation and reporting of residual disease in breast cancer clinical trials. In response the NCI convened the BIG-NABCG residual disease characterization-working group. Our working group published international standards of pathologic evaluation of residual disease after neoadjuvant systemic therapy for breast cancer clinical trials. Before our work there was no systematic analysis of what trials do and multidisciplinary consensus developed. We hope that this standardization effort will improve comparisons between clinical trials and enable accumulation of more robust evidence in controversial areas of practice such as specimen handling in the future.

Bossuyt V, Symmans WF. Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy. Ann Surg Oncol. 2016 Oct;23(10):3153-61. PubMed PMID: 27380637.

Bossuyt V, Hatzis C. The Neoadjuvant Model and Complete Pathologic Response in Breast Cancer: All or Nothing?. JAMA Oncol. 2016 Jun 1;2(6):760-1. PubMed PMID: 26914064.

Provenzano E, Bossuyt V, Viale G, Cameron D, Badve S, Denkert C, MacGrogan G, Penault-Llorca F, Boughey J, Curigliano G, Dixon JM, Esserman L, Fastner G, Kuehn T, Peintinger F, von Minckwitz G, White J, Yang W, Symmans WF. Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol. 2015 Sep;28(9):1185-201. PubMed PMID: 26205180.

Bossuyt V, Provenzano E, Symmans WF, Boughey JC, Coles C, Curigliano G, Dixon JM, Esserman LJ, Fastner G, Kuehn T, Peintinger F, von Minckwitz G, White J, Yang W, Badve S, Denkert C, MacGrogan G, Penault-Llorca F, Viale G, Cameron D. Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol. 2015 Jul;26(7):1280-91. PubMed PMID: 26019189; PubMed Central PMCID: PMC4804123.

I was a pathologist for a randomized, controlled trial evaluating the use of routine cavity shave margins (additional tissue circumferentially around the cavity left by partial mastectomy) for treatment of breast cancer. Many women who receive a diagnosis of early-stage breast cancer opt for breast-conserving surgery with partial mastectomy. Although the survival rate with such surgery is equivalent to that with total mastectomy, margin status is a critical determinant of local recurrence. Approximately 20 to 40% of patients have positive margins (margins positive for tumor) after partial mastectomy and require a second operation for margin clearance. In our randomized controlled trial cavity shaving halved the rates of positive margins and re-excision among patients with partial mastectomy without a negative effect on patient-perceived cosmesis.

Chagpar AB, Horowitz NR, Killelea BK, Tsangaris T, Longley P, Grizzle S, Loftus M, Li F, Butler M, Stavris K, Yao X, Harigopal M, Bossuyt V, Lannin DR, Pusztai L, Davidoff AJ, Gross CP. Economic Impact of Routine Cavity Margins Versus Standard Partial Mastectomy in Breast Cancer Patients: Results of a Randomized Controlled Trial. Ann Surg. 2016 May 17;PubMed PMID: 27192352.

Chagpar AB, Killelea BK, Tsangaris TN, Butler M, Stavris K, Li F, Yao X, Bossuyt V, Harigopal M, Lannin DR, Pusztai L, Horowitz NR. A Randomized, Controlled Trial of Cavity Shave Margins in Breast Cancer. N Engl J Med. 2015 Aug 6;373(6):503-10. PubMed PMID: 26028131.

Tumor infiltrating lymphocytes (TIL) have been associated with response to neoadjuvant therapy in breast cancer. However assessment of TILs is typically subjective, semiquantitative and unable to differentiate among subpopulations of lymphocytes. We developed a quantitative objective method for analyzing lymphocyte subpopulations expressing CD3, CD8 and CD20. This method offers potential advantage over existing lymphocyte quantification methods, including ability to assess subpopulations, objectivity and reproducibility.

Brown JR, Wimberly H, Lannin DR, Nixon C, Rimm DL, Bossuyt V. Multiplexed quantitative analysis of CD3, CD8, and CD20 predicts response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2014 Dec 1;20(23):5995-6005. PubMed PMID: 25255793; PubMed Central PMCID: PMC4252785.

Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunol Res. 2015 Apr;3(4):326-32. PubMed PMID: 25527356; PubMed Central PMCID: PMC4390454.

Because it is possible to evaluate tumor tissue before and after treatment and at multiple time points during treatment neoadjuvant breast cancer therapy (systemic treatment before surgical treatment) offers the opportunity to evaluate response to treatment after a few months as opposed to after several years with the traditional paradigm of surgery before systemic treatment. This is an ideal setting to try to identify predictors of response. I have helped identify such possible predictors of response: tumor infiltrating lymphocytes, PD-L1, a TGF-beta signature and quantitative HER2 or phospho- HER2. My specific role as a collaborator on these projects was evaluation of biopsies at different time points and assessment of the surgical specimen for response.

Cheng H, Bai Y, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, Harris LN, Rimm DL. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer. 2014 May 8;14:326. PubMed PMID: 24885187; PubMed Central PMCID: PMC4037428.

Brown JR, Wimberly H, Lannin DR, Nixon C, Rimm DL, Bossuyt V. Multiplexed quantitative analysis of CD3, CD8, and CD20 predicts response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2014 Dec 1;20(23):5995-6005. PubMed PMID: 25255793; PubMed Central PMCID: PMC4252785.

Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunol Res. 2015 Apr;3(4):326-32. PubMed PMID: 25527356; PubMed Central PMCID: PMC4390454.

Varadan V, Kamalakaran S, Gilmore H, Banerjee N, Janevski A, Miskimen KL, Williams N, Basavanhalli A, Madabhushi A, Lezon-Geyda K, Bossuyt V, Lannin DR, Abu-Khalaf M, Sikov W, Dimitrova N, Harris LN. Brief-exposure to preoperative bevacizumab reveals a TGF-β signature predictive of response in HER2-negative breast cancers. Int J Cancer. 2016 Feb 1;138(3):747-57. PubMed PMID: 26284485.

Breast cancer is a heterogeneous disease. While it is possible to identify subtypes of breast carcinoma on histologic examination, these subtypes become more clinically relevant when classification is augmented with molecular techniques. For example African American patients are at higher risk for triple negative (estrogen receptor, progesterone, and HER2 receptor negative) breast cancer compared to European Americans. When we compared gene expression profiles of triple negative tumors of European and African American patients. Tumors from African American patients were more likely basal-like whereas transcriptional features of many tumors from European American patients corresponded to mesenchymal-like or luminal androgen receptor driven subtypes. It is important to consider these differences when selecting targeted treatments for these patients.

Lindner R, Sullivan C, Offor O, Lezon-Geyda K, Halligan K, Fischbach N, Shah M, Bossuyt V, Schulz V, Tuck DP, Harris LN. Molecular phenotypes in triple negative breast cancer from African American patients suggest targets for therapy. PLoS One. 2013;8(11):e71915. PubMed PMID: 24260093; PubMed Central PMCID: PMC3832509.

I was the recipient of a Lion Heart Fund for Cancer Research award in 2014 for “a pilot study to identify a gene signature of age related involution in healthy breast tissue”.

Selected Publications

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Contact Info

Veerle Bossuyt, MD
Patient Care Location
Yale PathologyYale New Haven Hospital
20 York Street

New Haven, CT 06510
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Office Location
Department of PathologyBrady Memorial Laboratory
310 Cedar Street, Ste BML 254C

New Haven, CT 06510
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Mailing Address
310 Cedar Street
PO Box 208023

New Haven, CT 06520-8023