Pathology of Breast Carcinomas After Neoadjuvant Chemotherapy: An Overview With Recommendations on Specimen Processing and Reporting

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					                                                              Review Article




                         Pathology of Breast Carcinomas After
                             Neoadjuvant Chemotherapy
   An Overview With Recommendations on Specimen Processing and Reporting
                                               Sunati Sahoo, MD; Susan C. Lester, MD, PhD

● Context.—Currently, more women are being treated with                   neoadjuvant therapy and the authors’ personal experience
chemotherapy or hormonal agents before surgery (neoad-                    with the clinical and pathologic characteristics of cases
juvant chemoendocrine therapy) for earlier-stage operable                 from each of the authors’ own institutions.
breast carcinoma. The pathologic examination of these                        Conclusions.—Pathologists play a key role in the evalu-
specimens can be quite challenging.                                       ation of pathologic response, which is extremely important
  Objective.—To give an overview of (1) pathologic chang-                 as a prognostic factor for individual patients, as a short-
es that occur during treatment, (2) systems for evaluating                term endpoint for clinical trials, and as an adjunct for re-
response to treatment, and (3) recommendations for path-                  search studies. Therefore, surgical pathologists must be fa-
ologic examination and reporting of such cases.                           miliar with the gross examination, sampling, and reporting
  Data Sources.—The recommendations are based on the                      of breast carcinomas after neoadjuvant therapy.
review of selected literature on breast carcinoma after                      (Arch Pathol Lab Med. 2009;133:633–642)

                 BACKGROUND AND SCOPE                                     sented at this meeting are publicly available at http://
                                                                          ctep.cancer.gov/bcmeeting.
   Neoadjuvant therapy (NAT), also termed primary or                        Published clinical trials have shown that systemic ther-
preoperative therapy, refers to the treatment of patients                 apy before or after surgery gives identical results for lo-
with systemic agents before definitive surgical removal of                 coregional control and metastasis-free survival.2,3,6 How-
a carcinoma. It was originally used as a standard treat-                  ever, the following are several major advantages of neoad-
ment for inflammatory and inoperable locally advanced                      juvant therapy.
breast cancers.1,2 Diagnosis was typically made by fine-
needle aspiration. Therefore, pathologic information about                   1. The efficacy of systemic therapy can be assessed in
the carcinoma (eg, type and grade) and information for                    vivo. The response, or nonresponse, of cancers can be de-
staging (eg, size and lymph node status) was limited. The                 termined in individual patients. In all studies, compared
combination of image-guided core needle biopsy, sentinel                  to poor responders, patients who achieve a good clinical
lymph node biopsy (or fine-needle aspiration of a palpable                 response have improved long-term disease-free survival
or suspicious node), and new breast imaging modalities                    and overall survival, indicating that clinical response can
(such as magnetic resonance imaging) have substantially                   be used as an early surrogate of outcome. Patients who
increased the ability to accurately classify and stage car-               achieve a pathologic complete response (pCR), that is, no
cinomas before surgical excision. Thus, increasing num-                   residual invasive carcinoma in the breast or lymph nodes,
bers of women with earlier-stage operable breast cancers                  have an excellent prognosis.2,7–15 Information about re-
are now being treated with chemotherapy or hormonal                       sponse can also be used to modify or change treatment
agents before surgery.3–5 Recently, a detailed review on                  for patients whose carcinomas show little or no change
‘‘Preoperative Therapy in Invasive Breast Cancer: Review-                 after initial treatment.
ing the State of the Science and Exploring New Research                      2. Tumor response is a short-term endpoint for clinical
Directions’’ was conducted at the 2007 National Cancer                    trials. After a breast carcinoma is surgically removed, the
Institute State of the Science meeting. The materials pre-                next endpoint for a clinical trial is recurrence or death.
                                                                          However, these events may not occur for many years or
                                                                          even decades. In addition, if a patient does well, it cannot
  Accepted for publication August 7, 2008.                                be determined if this outcome is due to the effectiveness
  From the Department of Pathology, Brigham and Women’s Hospital,         of the systemic treatment or because the carcinoma was
Boston, Mass (Dr Lester); and the Department of Pathology, University     completely removed by surgery. Tumor response provides
of Louisville, Louisville, Ky (Dr Sahoo).                                 important clinical information within months, which can
  The authors have no relevant financial interest in 
				
DOCUMENT INFO
Description: CONTEXT: Currently, more women are being treated with chemotherapy or hormonal agents before surgery (neoadjuvant chemoendocrine therapy) for earlier-stage operable breast carcinoma. The pathologic examination of these specimens can be quite challenging. OBJECTIVE: To give an overview of (1) pathologic changes that occur during treatment, (2) systems for evaluating response to treatment, and (3) recommendations for pathologic examination and reporting of such cases. DATA SOURCES: The recommendations are based on the review of selected literature on breast carcinoma after neoadjuvant therapy and the authors' personal experience with the clinical and pathologic characteristics of cases from each of the authors' own institutions. CONCLUSIONS: Pathologists play a key role in the evaluation of pathologic response, which is extremely important as a prognostic factor for individual patients, as a short-term endpoint for clinical trials, and as an adjunct for research studies. Therefore, surgical pathologists must be familiar with the gross examination, sampling, and reporting of breast carcinomas after neoadjuvant therapy.
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