Neoadjuvant Chemotherapy for Breast Cancer: Moving Beyond Pathological Complete Response in the Molecular Age

Abstract

<p>This review focuses on neoadjuvant chemotherapy for breast cancer which introduces practical issues for pathologists, including predicting response, optimising specimen handling, size measurement and assessment of residual disease, and recent advances in management of the axilla. The role of neoadjuvant chemotherapy in breast cancer is increasing, and it has become standard of care for high risk Human Epidermal Growth Factor Receptor 2 positive and triple negative breast cancers. The benefits of the neoadjuvant approach extend beyond pathological complete response to tumour downstaging permitting conservative surgi- cal options in the breast and axilla, and assessment of response provides valuable prognostic information to enable escalation and de-escalation of adjuvant therapy to optimise oncological outcomes. Hence histopathologists play a vital role in patient management in the neoadjuvant setting. Optimal patient selection for neoadjuvant chemotherapy requires consideration of pre- treatment histopathological and molecular tumour characteristics. Post chemotherapy, tumour staging can be challenging, and changes in criteria for measurement of primary tumour and metastases in the 7th and 8th editions of the TNM have led to confu- sion amongst pathologists. This review offers practical guidance on specimen handling and measurement of lesion size. Mov- ing forwards more detailed information on degree of response will be required for adjuvant therapy decision making, and the Residual Cancer Burden is emerging as the preferred method for quantifying residual disease not just within clinical trials but in routine practice. Recent advances in management of the axilla are discussed, including the significance of minimal residual disease in the form of isolated tumour cells and micrometastases which portend a worse prognosis in the neoadjuvant setting.</p><p><strong>Conclusion</strong>. Neoadjuvant chemotherapy now forms part of routine breast cancer management, and detailed histopathological assessment and an understanding of the importance of molecular tumour biology is essential for clinical decision making.</p>

Pathology of neoadjuvant therapy and immunotherapy testing for breast cancer

“…Accurate diagnosis of pCR, and determination of the presence and quantification of residual disease, is of prognostic importance and is used to make decisions regarding the need for further local and systemic adjuvant therapy. 45 Chemotherapy also induces changes in the surrounding benign breast tissue. 15,33,46 The background breast often shows pronounced lobular atrophy with associated hyalinisation and sclerosis of remaining acinar units (Figure 4).…”

“…If there is any doubt that the correct area has been sampled, or if inadequate clinical information has been provided to accurately locate and sample the previous tumour site, then this should be stated in the report. Accurate diagnosis of pCR, and determination of the presence and quantification of residual disease, is of prognostic importance and is used to make decisions regarding the need for further local and systemic adjuvant therapy 45 …”

Ability of dynamic contrast-enhanced magnetic resonance imaging to determine axillary sentinel lymph node status in patients with breast cancer

“…With the advent of novel tracers and pathologic and histologic techniques, the most important nodes, namely, the SLNs, now undergo a more thorough and standardized histopathologic examination, which has improved the rate of detection of isolated tumor cells and micrometastases in these nodes [10][11][12][13]. More recent research has reported their prognostic and survival impact, and adjuvant systemic treatment is recommended [14][15][16]. Magnetic resonance imaging (MRI) is a noninvasive technique that can offer valuable information regarding tissues and organs.…”

Aldehyde dehydrogenase 2 polymorphism is associated with chemotherapy‐related cognitive impairment in patients with breast cancer who receive chemotherapy

“… 4 , 5 , 6 Patients with breast cancer often need multiple chemotherapy treatments. 7 , 8 The physical health of patients with breast cancer is severely affected by the somatic side effects of chemotherapy. 9 However, a cognitive decline caused by chemotherapy also affects these patients' quality of life (QOL).…”

“…In China, the incidence of breast cancer is 7.33%, which ranks first among malignant tumours in females, with a death rate of approximately 6.9% 4–6 . Patients with breast cancer often need multiple chemotherapy treatments 7,8 . The physical health of patients with breast cancer is severely affected by the somatic side effects of chemotherapy 9 .…”