Breast cancer

Neoadjuvant chemotherapy

Last author update: 1 April 2017
Last staff update: 5 May 2022

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PubMed Search: breast chemotherapy effect

Emily S. Reisenbichler, M.D.
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Cite this page: Reisenbichler ES Neoadjuvant chemotherapy. website. Accessed July 6th, 2022.
Definition / general
  • Histologic findings for patients who undergo neoadjuvant (preoperative) chemotherapy (delivery of chemotherapeutic treatment after a biopsy diagnosis but prior to definitive surgical management)
  • Evaluation of tumor response to chemotherapy provides prognostic information
  • A complete pathologic response (pCR) is defined as no residual invasive or metastatic tumor (ypTisN0 or ypT0N0)
Essential features
  • Chemotherapeutic effects can be seen in the primary breast tumor and axillary lymph node metastases as well as in normal breast tissue
  • Benefits of neoadjuvent chemotherapy include the possibility to render inoperable tumors operable and providing important prognostic information based on response to therapy
  • The "Residual Cancer Burden" method is preferred for evaluating tumor response to chemotherapy
  • Neoadjuvant chemotherapy is defined as the delivery of chemotherapy prior to surgical resection
  • Standardized definition of pathological complete response (pCR) includes residual DCIS (either ypT0/isypN0 or ypT0ypN0)
Clinical features
  • Candidates for preoperative therapy include those with inoperable breast cancer, occult primary tumors with axillary metastases and those with a large tumor desiring breast conservation
  • Clinical signs of response to neoadjuvant chemotherapy include difficulty palpating the tumor due to tumor softening and reduction of tumor size and cellularity
Radiology description
Prognostic factors
  • Most useful prognostic information is obtained from evaluating response to preoperative therapy in patients with HER2 positive (nonluminal; ER / PR negative, all grades), triple negative (ER / PR and HER2 negative, all grades) or Luminal B / HER2 negative (ER / PR positive, HER2 negative, grade 3) tumors (J Clin Oncol 2012;30:1796)
  • Quantification of residual tumor using the Residual Cancer Burden (RCB) calculator has been clinically validated with long term follow up data and increasing RCB score is a significant predictor of distant relapse free survival (J Clin Oncol 2007;25:4414)
  • Posttreatment staging (Amin: AJCC Cancer Staging Manual, 8th Edition, 2017):
    • Primary tumor stage (ypT) based on largest contiguous focus of residual tumor; do not include intervening fibrous tissue; often requires the "m" modifier to indicate multiple residual foci within the tumor bed
    • Lymph node stage (ypN): deposits measured like primary tumor, largest contiguous focus not including associated fibrosis
Gross description
  • In cases of poor response, tumor will demonstrate the typical, firm, gritty, spiculated appearance
  • In cases of good or even complete pathologic response, the tumor bed may be soft and difficult to distinguish from normal fibrous breast tissue
  • International working group guidelines strongly recommend taking gross pictures with a record of submitted sections to "map out" residual disease seen microscopically (Mod Pathol 2015;28:1185)
  • Sampling extent should be determined by the pretreatment tumor size (FDA recommends a minimum of one block per cm of pretreatment tumor size)
  • Sampling should include any grossly residual disease and area of the biopsy clip with submission of a complete cross section of tumor (up to 5 blocks for large tumors) for calculation of cellularity
Gross images

Contributed by Emily S. Reisenbichler, M.D.

Complete response to neoadjuvant chemotherapy

No significant response to neoadjuvant chemotherapy

Microscopic (histologic) description
  • Loss of tumor may occur as concentric shrinking of the tumor or as scattered loss / drop out of tumor cells
  • Tumor is replaced by loose fibrous tissue containing a variable infiltration of histiocytes, lymphocytes, giant cells, hemosiderin and vascular proliferation (similar changes are seen in lymph nodes)
  • Changes in normal breast tissue may include lobular atrophy, lobular cellular atypia and fibrous stromal involution
  • Multiple methods for evaluating tumor response to chemotherapy have been described:
Microscopic (histologic) images

Contributed by Emily S. Reisenbichler, M.D.

No residual invasive or in situ tumor

Small clusters of residual invasive tumor cells

Board review style question #1
Which of these constitutes a Pathologic complete response?

  1. A fibrous tumor bed containing a single focus of tumor cells present within lymphatics but no invasive or in situ tumor.
  2. A fibrous tumor bed containing less than 200 invasive tumor cells.
  3. A fibrous tumor bed containing no invasive tumor and only isolated tumor cells seen in one axillary lymph node.
  4. A fibrous tumor bed with a single focus of residual ductal carcinoma in situ (DCIS) and isolated tumor cells in a single axillary lymph node.
  5. A fibrous tumor bed with extensive residual ductal carcinoma in situ (DCIS) spanning greater than 5 cm.
Board review style answer #1
E. A fibrous tumor bed with extensive residual ductal carcinoma in situ (DCIS) spanning greater than 5 cm. A complete pathologic response (pCR) is defined as no residual invasive or metastatic tumor. This includes the presence of any residual invasive tumor in the stroma or lymphatics or metastatic tumor in lymph nodes. Regardless of extent, the presence of residual DCIS, in the absence of any other carcinoma, is consistent with a complete pathologic response.

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Reference: Chemotherapy
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