Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Its cells do not have estrogen or progesterone receptors and do not produce excess amounts of a protein called HER2. This “triple-negative” status means it will not respond to hormonal therapies or drugs that target HER2. For this reason, treatment strategies involve chemotherapy. A measure of treatment success is the pathologic complete response (pCR), a significant indicator of a patient’s long-term prognosis.
Understanding Pathologic Complete Response
For many individuals with early-stage TNBC, treatment begins with neoadjuvant therapy, which is chemotherapy administered before surgery. The main goal is to shrink the tumor, making it easier to remove surgically, and to eliminate any cancer cells that may have escaped the primary tumor. It also provides an early indication of how well the cancer responds to a particular treatment regimen.
After neoadjuvant therapy and surgery, a pathologist examines the removed tissue. A pathologic complete response is achieved when this examination reveals no remaining invasive cancer cells in either the breast or the nearby lymph nodes. This is a direct measure of how effectively the preoperative treatment has worked. The pCR is an outcome of treatment, not a diagnosis, and helps oncologists guide future treatment decisions.
The Prognostic Significance of Achieving pCR
Achieving a pCR is a strong predictor of a favorable long-term outcome for patients with TNBC. When neoadjuvant chemotherapy successfully eradicates all invasive cancer from the breast and lymph nodes, the prognosis improves substantially. This outcome is linked to a significantly lower risk of recurrence and reflected in higher rates of both event-free survival (EFS) and overall survival (OS).
Meta-analyses of clinical trials show that patients who attain pCR have a 5-year event-free survival rate of approximately 92% and a 10-year EFS around 87%. In contrast, those who do not achieve pCR face a much higher likelihood of their cancer returning. This makes achieving pCR a primary goal of neoadjuvant treatment for TNBC.
The benefit of achieving a pCR is so significant that it can change a patient’s long-term outlook to be comparable to that of individuals with less aggressive forms of breast cancer. The prognosis associated with pCR holds true regardless of the specific chemotherapy regimen used to achieve it.
Prognosis with Residual Disease
When a pathologic complete response is not achieved after neoadjuvant therapy, it means there is residual disease (RD). A pathologist identifies remaining invasive cancer cells in the breast tissue or lymph nodes. This finding indicates the cancer was not completely eliminated and is associated with a higher risk of recurrence and a less favorable prognosis.
Pathologists use the Residual Cancer Burden (RCB) index to quantify the amount of leftover cancer. The RCB index considers the size of the remaining tumor bed, the percentage of cancer cells, and the extent of cancer in the lymph nodes. This information is used to categorize the residual disease into different classes, such as RCB-I, RCB-II, and RCB-III.
The amount of residual disease, as measured by the RCB index, directly correlates with prognosis. A smaller amount of residual disease (RCB-I) carries a better prognosis than extensive residual disease (RCB-III). For example, patients with an RCB of 0 or I have a recurrence-free survival rate of around 94%, while those with an RCB of II or III have a rate closer to 68%. This assessment helps oncologists tailor subsequent treatment plans.
Beyond pCR: Other Prognostic Factors
While the response to neoadjuvant therapy is a powerful indicator, other factors from the initial diagnosis also shape the prognosis. The initial stage of the cancer is a fundamental prognostic factor. This is determined by the size of the original tumor and whether it had spread to nearby lymph nodes before any treatment began. A larger tumor or one that has already metastasized is associated with a more challenging prognosis.
The grade of the tumor, which describes how abnormal the cancer cells appear, also provides prognostic information. Higher-grade tumors, where the cells look very different from normal cells, tend to be more aggressive. Additionally, inherited genetic mutations, such as those in the BRCA1 and BRCA2 genes, can influence both the risk of developing TNBC and its prognosis.