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Neoadjuvant Therapy in the Treatment of Breast Cancer

Neoadjuvant systemic therapy in breast cancer treatment was initially utilized for inoperable disease. However, several randomized prospective studies have demonstrated comparable survival with adjuvant chemotherapy in early-stage, operable breast cancer while also decreasing tumor size facilitating breast conservation without significant increases in local recurrence. Response to therapy can predict outcome, with improved survival associated with pathologic complete response (pCR). Triple negative and HER2-positive subtypes show increased pCR rates. A multidisciplinary approach is necessary with neoadjuvant treatment. This can improve rates of breast conservation, provide insights into tumor biology and predict patient outcomes.

Identification of Patients With Documented Pathologic Complete Response in the Breast After Neoadjuvant Chemotherapy for Omission of Axillary Surgery

Importance A pathologic complete response (pCR; no invasive or in situ cancer) occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative (TN) breast cancer. The need for surgery if percutaneous biopsy of the breast after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter referred to as breast pCR) has been questioned, and appropriate management of the axilla in such patients is unknown. Objective To identify patients among exceptional responders to NCT with a low risk for axillary metastases when breast pCR is documented who may be eligible for an omission of surgery clinical trial design. Design, Setting, and Participants This prospective cohort study at a single-institution academic national comprehensive cancer center included 527 consecutive patients with HER2+/TN (T1/T2 and N0/N1) cancer treated with NCT followed by standard breast and nodal surgery from January 1, 2010, through December 31, 2014. Main Outcomes and Measures Patients who achieved a breast pCR were compared with patients who did not based on subtype, initial ultrasonographic findings, and documented pathologic nodal status. Incidence of positive findings for nodal disease on final pathologic review was calculated for patients with and without pCR and compared using relative risk ratios with 95% CIs. Results The analysis included 527 patients (median age, 51 [range, 23-84] years). Among 290 patients with initial nodal ultrasonography showing N0 disease, 116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease, 69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence of residual nodal disease (P < .01). Patients without a breast pCR had a relative risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8; P < .001) compared with those with a breast pCR. Conclusions and Relevance Breast pCR is highly correlated with nodal status after NCT, and the risk for missing nodal metastases without axillary surgery in this cohort is extremely low. These data provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guided biopsy indicates a breast pCR.

A Clinical Feasibility Trial for Identification of Exceptional Responders in Whom Breast Cancer Surgery Can Be Eliminated Following Neoadjuvant Systemic Therapy

Objective: To determine the accuracy of fine-needle aspiration (FNA) and vacuum-assisted core biopsy (VACB) in assessing the presence of residual cancer in the breast after neoadjuvant systemic therapy (NST). Summary Background Data: Pathologic complete response (pCR) rates after NST have improved dramatically, suggesting that surgery might be avoided in some patients. Safe avoidance of surgery would require accurate confirmation of no residual invasive/in situ carcinoma. Methods: Forty patients with T1-3N0-3 triple-negative or HER2-positive cancer receiving NST were enrolled in this single-center prospective trial. Patients underwent ultrasound-guided or mammography-guided FNA and VACB of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting residual breast disease after NST. Results: Median initial clinical tumor size was 3.3 cm (range, 1.2–7.0 cm); 16 patients (40%) had biopsy-proven nodal metastases. After NST, median clinical tumor size was 1.1 cm (range, 0–4.2 cm). Nineteen patients (47.5%) had a breast pCR and were concordant with pathologic nodal status in 97.5%. Combined FNA/VACB demonstrated an accuracy of 98% (95% CI, 87%–100%), false-negative rate of 5% (95% CI, 0%–24%), and negative predictive value of 95% (95% CI, 75%–100%) in predicting residual breast cancer. VACB alone was more accurate than FNA alone (P = 0.011). Conclusions: After NST, image-guided FNA/VACB can accurately identify patients with a breast pCR. Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

Combining clinical and pathologic staging variables has prognostic value in predicting local-regional recurrence following neoadjuvant chemotherapy for breast cancer

Objective: The current study was undertaken to determine if the CPS+EG score could stratify patients with respect to local-regional recurrence (LRR). Background: We previously defined and validated a novel breast cancer staging system incorporating the American Joint Committee on Cancer clinical stage (CS), final pathologic stage (PS), estrogen receptor status (E), and nuclear grade (G) (CPS+EG score). The score is associated with disease-specific survival outcomes in patients treated with neoadjuvant chemotherapy. Methods: Patients receiving neoadjuvant chemotherapy between 1997 and 2005 were identified and clinicopathologic data were used to determine the CPS+EG score. Type of local therapy, breast-conserving therapy, mastectomy alone, or mastectomy followed by postmastectomy radiation therapy was recorded. Multivariate analysis, including CPS+EG score and local therapy, was performed to evaluate for association with LRR. Results: Of 1697 patients, breast conserving therapy was performed in 656 (39%), mastectomy in 297 (17%) and mastectomy + postmastectomy radiation therapy in 744 (44%). At a median follow-up of 49 months, the crude incidence of LRR was 6.5%. Freedom from LRR at 5 years ranged from 86% to 97% by clinical stage, 86% to 97% by pathologic stage, and 71% to 99% by CPS+EG score. On multivariate analysis, CPS+EG score and surgery type were independently associated with LRR, with increased risk among patients with CPS+EG scores of 3 or greater (HR 1.94, 95% CI 1.04–3.63) or mastectomy alone (HR 2.14, 95% CI 1.26–3.63). Conclusions: The CPS+EG staging system better stratifies patients with respect to LRR after neoadjuvant chemotherapy than presenting clinical stage or final pathologic stage. For CPS+EG scores ≥3, use of postmastectomy radiation therapy decreases the likelihood of LRR after mastectomy.

International consensus on the clinical management of Inflammatory Breast Cancer from the Morgan Welch Inflammatory Breast Cancer research program 10th anniversary conference

National and international experts in inflammatory breast cancer (IBC) from high-volume centers treating IBC recently convened at the 10th Anniversary Conference of the Morgan Welch Inflammatory Breast Cancer Research Program at The University of Texas MD Anderson Cancer Center in Houston Texas. A consensus on the clinical management of patients with IBC was discussed, summarized, and subsequently reviewed. All participants at the conference (patients, advocates, researchers, trainees, and clinicians) were queried using the MDRing electronic survey on key management issues. A summary of the expert consensus and participant voting is presented. Bilateral breast and nodal evaluation, breast magnetic resonance imaging, positron emission tomography/computed tomography, and medical photographs were endorsed as optimal. Neoadjuvant systemic therapy, modified radical mastectomy and level I and II ipsilateral axillary node dissection, post-mastectomy radiotherapy, adjuvant targeted therapy and hormonal therapy as indicated, and delayed reconstruction were agreed-upon fundamental premises of standard non-protocol-based treatment for IBC. Consideration for local-regional therapy in de novo stage IV IBC was endorsed to provide local control whenever feasible. Variation across centers and special circumstances were discussed.

Role of Operative Management in Stage IV Breast Cancer

The role of operative therapy in stage IV breast cancer continues to evolve with advances in therapy and improvements in survival among this population. Traditionally surgery was performed with palliative intent to alleviate symptoms related to the intact breast primary. Several retrospective studies have challenged this paradigm, demonstrating survival advantage with surgery in de novo metastatic disease. Prospective studies are ongoing and maturing data. A comprehensive approach to local therapy following systemic therapy may be beneficial to achieve improved survival outcome associated with stage IV- no evidence of disease and to decrease local failure in inflammatory breast cancer.

Training of breast surgical oncologists

Breast surgical oncology is a defined sub-specialty of general surgery with focus on the surgical management of breast disease and malignancy within a multidisciplinary context. Much of the training of breast surgical oncologists in the United States exists within a fellowship training structure with oversight and approval by the Society of Surgical Oncology (SSO). Rapid continuous changes in breast oncology practice have further substantiated dedicated expertise in breast surgical oncology. Training programs are structured to develop proficiency in fellows for advanced surgical techniques and clinical decision-making as well as exposure to the multidisciplinary aspects of breast cancer management. Components of a successful program include an intense multidisciplinary curriculum, engagement in clinical research and attention to strong mentorship. National curriculum and training requirements as well as supplemental resources assist in standardizing the fellowship experience. As surgical training and the field of breast oncology continues to evolve, so do fellowship training programs to ensure high quality breast surgical oncologists equipped to deliver high quality evidence based patient care while continuing to drive future research and trainee education.