Breast Cancer Response to Pre-Surgery Chemotherapy May Suggest its Benefit in Long-term

Breast Cancer News
July 3, 2014
Nicole Katze, MA, Editor and Manager, Content Development
Reviewed By: 
Kathryn J. Ruddy, MD, MPH

Showing no sign of invasive cancer in the breast or nearby lymph nodes after treatment with pre-surgery chemotherapy may lead to longer survival, an analysis of 12 international studies suggests. This was most true for those with hormone receptor-negative, HR-negative, breast cancers.

Background and Goals

Pre-surgery, or neoadjuvant, chemotherapy is becoming more widely used to treat early-stage breast cancer because it shows potential in controlling tumor growth and ridding the body of cancer cells. Doctors believe the increase in the number of clinical trials testing neoadjuvant chemotherapy could lead to faster FDA approval of new effective medicines that typically would need to be approved for metastatic breast cancer first.

In neoadjuvant trials, researchers assess the therapy’s effect on pathological complete response, pCR, which is often defined as showing no sign of invasive disease in the breast or nearby lymph nodes at the time of surgery. Yet, there is no agreed on definition of pCR (some studies also require no non-invasive cancer, and some focus only on what is found in the breast rather than in the breast and lymph nodes).

There is also no direct understanding of the relation between pCR and long-term outcomes, such as event-free survival, EFS,and overall survival, OS, which are more often assessed in studies of medicines used after surgery.

To explore these issues, the U.S. Food and Drug Administration formed Collaborative Trials in Neoadjuvant Breast Cancer, CTNeoBC. The group pooled data from as many neoadjuvant trials as possible to:

  • see how pCR relates to EFS and OS
    • EFS was defined as the time from joining the trial to the earliest return or worsening of the disease
    • OS was defined as the time from joining the trial to death from any cause
  • agree on and recommend a standard definition of pCR that is most closely associated with EFS and OS
  • identify for which tumor subtypes pCR may relate to long-term outcomes
  • assess whether trials that produced higher rates of pCR also produced longer EFS or OS


The researchers analyzed data on 11,955 people treated with neoadjuvant chemotherapy. They included only trials that:

  • enrolled at least 200 people treated with neoadjuvant chemotherapy and standard surgery
  • collected data on pCR, EFS and OS
  • followed those who took part for at least 3 years

Researchers compared the three most commonly used definitions of pCR to see how each was related to EFS and OS. These definitions were:

  • free of cancer in the breast and lymph nodes at the time of surgery, with no signs of DCIS
  • free of cancer in the breast and lymph nodes at the time of surgery, with or without signs of DCIS
  • free of cancer in the breast at the time of surgery, with or without signs of cancer cells in the lymph nodes or of DCIS

DCIS is ductal carcinoma in situ, also called stage 0 cancer.


Overall, the team found that:

  • pCR did not occur often, and was seen in only 13-18 percent of participants depending on the definition of pCR
    • the more stringent the definition of pCR, the less often it happened
  • EFS and OS were longer in people who had no sign of cancer in both the breast and lymph nodes than in people who were only clear of cancer in the breast

In addition,

pCR occurred more often in triple-negative and HER2-positive cancers, which tend to grow and spread more quickly than others.

  • In HER2-positive disease, pCR was more common in HR-negative tumors and when trastuzumab was given

In assessing the relation between pCR, EFS and OS, researchers found:

  • people with pCR after chemotherapy had longer EFS and OS than people who had some cancer cells left at surgery
  • pCR was linked to longer EFS and OS in HR-positive, HER2-negative disease, especially when tumors were high grade
  • pCR was linked to better long-term survival outcomes in HER2-positive disease, especially when tumors were HR-negative and treated with trastuzumab
  • pCR was strongly linked to longer EFS and OS in triple-negative cancers

What This Means for You

This study is the first to assess the relation between pCR, EFS and OS on a large scale. It suggests that watching tumor response to neoadjuvant chemotherapy may help doctors predict long-term breast cancer outcomes, especially for those with HR-negative disease.

If you are newly diagnosed and creating a treatment plan with your doctor, it makes sense to ask whether neoadjuvant chemotherapy will be part of your care. At this time, neoadjuvant chemotherapy isn’t always the best option for early-stage breast cancer, but is often considered to shrink the tumor before surgery. Your doctor will be able to recommend the best treatment for you.

Cortazar, P, Zhang, L, Untch, M, Mehta, K, Costantino, J, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. The Lancet. 2014; doi:10.1016/S0140-6736(13)62422-8

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