Anita Mamtani

Axillary Dissection and Nodal Irradiation Can Be Avoided for Most Node-positive Z0011-eligible Breast Cancers: A Prospective Validation Study of 793 Patients.

Objective: To determine rates of axillary dissection (ALND) and nodal recurrence in patients eligible for ACOSOG Z0011. Background: Z0011 demonstrated that patients with cT1-2N0 breast cancers and 1 to 2 involved sentinel lymph nodes (SLNs) having breast-conserving therapy had no difference in locoregional recurrence or survival after SLN biopsy alone or ALND. The generalizability of the results and importance of nodal radiotherapy (RT) is unclear. Methods: Patients eligible for Z0011 had SLN biopsy alone. Prospectively defined indications for ALND were metastases in ≥3 SLNs or gross extracapsular extension. Axillary imaging was not routine. SLN and ALND groups and radiation fields were compared with chi-square and t tests. Cumulative incidence of recurrences was estimated with competing risk analysis. Results: From August 2010 to December 2016, 793 patients met Z0011 eligibility criteria and had SLN metastases. Among them, 130 (16%) had ALND; ALND did not vary based on age, estrogen receptor, progesterone receptor, or HER2 status. Five-year event-free survival after SLN alone was 93% with no isolated axillary recurrences. Cumulative 5-year rates of breast + nodal and nodal + distant recurrence were each 0.7%. In 484 SLN-only patients with known RT fields (103 prone, 280 supine tangent, 101 breast + nodes) and follow-up ≥12 months, the 5-year cumulative nodal recurrence rate was 1% and did not differ significantly by RT fields. Conclusions: We confirm that even without preoperative axillary imaging or routine use of nodal RT, ALND can be avoided in a large majority of Z0011-eligible patients with excellent regional control. This approach has the potential to spare substantial numbers of women the morbidity of ALND.

Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2‐Positive Early Stage Breast Cancer: A Single Center Experience

OBJECTIVES Trastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 -positive patients. A retrospective analysis was performed of patients treated with dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported. METHODS An electronic medical record review was conducted of patients treated with HP-based therapy in the neoadjuvant setting from September 1, 2013, to March 1, 2015. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as total (tpCR, ypT0/is ypN0), German Breast Group (GBG) pCR (ypT0 ypN0), breast pCR (bpCR) with in situ disease (ypT0/is) and without in situ disease (ypT0), and explored axillary pCR (ypN0). RESULTS Charts from 66 patients were reviewed, and 57 patients were evaluable for pCR. Median age was 46 years (range 26-68 years). Median tumor size was 4 cm. Of 57 patients, 53 (93%) had operable breast cancer (T1-3, N0-1, M0). Three patients (5.3%) had locally advanced disease (T2-3, N2-3, M0 or T4a-c, any N, M0), and 1 (1.7%) had inflammatory breast cancer (T4d, any N, M0). Overall, 44 (77%) and 13 (23%) had hormone receptor (HR)-positive and negative diseases, respectively. Median numbers of cycles of neoadjuvant treatment were as follows: AC (4, range 1-4), T (4, range 1-4), trastuzumab (6, range 3-8), and pertuzumab (6, range 2-8). In these 57 patients, the rates of tpCR and bpCR with in situ disease were demonstrated in 41/57 (72%) patients, and the rates of GBG pCR and bpCR without in situ disease were found in 30/57 (53%) patients. Of 26 patients with biopsy-proven lymph nodal involvement, axillary pCR occurred in 22 (85%) patients. CONCLUSION At a single center, the tpCR and GBG pCR rates of dd AC followed by THP are high at 72% and 53%, respectively. The Oncologist 2017;22:139-143Implications for Practice: This is the first study describing the role of doxorubicin and cyclophosphamide followed by paclitaxel and dual anti-HER2 therapy with trastuzumab and pertuzumab (ACTHP) in patients with early stage HER2-positive breast cancer. Total (breast + lymph node) pathological complete remission (pCR) remission (ypT0/is ypN0) and German Breast Group pCR rates (ypT0/ ypN0) were high at 72% and 53%, respectively, with the ACTHP regimen. Rate of axillary clearance in patients with known axillary involvement was high at 85%, which may translate into less extensive axillary surgeries in this subset in the future.

Lobular Breast Cancer: Different Disease, Different Algorithms?

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer, with a unique pathogenesis and distinct clinical biology. ILCs display a characteristic loss of E-cadherin, are largely estrogen receptor positive, HER2 negative, and low to intermediate grade. These features portend a favorable prognosis, but there is a tendency for late recurrences and atypical metastases. ILCs tend to be insidious and infiltrative, which can pose a challenge for diagnosis, and emerging data suggest they may have a propensity for a differing response to standard therapies.

Are there patients with T1 to T2, lymph node-negative breast cancer who are "high-risk" for locoregional disease recurrence?

Indications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node‐negative (N0) breast cancer with “high‐risk” features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10‐year disease‐free survival with lymph node irradiation included patients with high‐risk N0 disease, but, to the authors’ knowledge, benefits in patients receiving modern systemic therapy are uncertain.

Why Are There So Many Mastectomies in the United States

Breast-conserving therapy (BCT) and mastectomy result in equivalent long-term survival. Locoregional recurrence rates after BCT have decreased over time and are now similar to those after mastectomy. Contralateral breast cancer rates are declining as well owing to the widespread use of adjuvant systemic therapy. Despite these improved outcomes, increasing rates of bilateral mastectomy for unilateral cancer have been observed in the United States. Medical indications for mastectomy are well defined and present in a minority of patients, and women at increased risk for contralateral cancer are a small proportion of the breast cancer population. Evidence indicates that increasing use of mastectomy is a patient-driven trend that is most pronounced among younger, educated, and well-insured women, and reflects fear of recurrence and in some cases misunderstanding of future cancer risks. Although satisfaction levels are generally high among patients choosing contralateral prophylactic mastectomy, complications and procedure extent may be underestimated. Improved communication strategies are essential to facilitate this complex decision-making process.

Targeted Therapy and Local Control: The Dynamic Duo

Breast cancer is a heterogeneous entity, comprised of several distinct molecular subtypes with differing genetic profiles and resultant prognostic implications. It has become increasingly evident that tumor biology is the key to understanding not only the pathogenesis of breast cancer but also to tailoring therapies to optimize outcomes. Classically, the hormone receptor-positive subtypes have the most favorable outcomes, whereas the triple-negative (TN) and human epidermal growth factor receptor 2-positive (HER2?) subtypes are ascribed higher rates of locoregional recurrence (LRR) and distant metastases, shown in a number of studies and a large systematic review. The development of trastuzumab serves as a premier example of targeting tumor biology for therapeutic gain. Trastuzumab is a humanized monoclonal antibody that binds to and interferes with the HER2-mediated signaling cascade, inhibiting proliferation and resulting in cell death. Initially used in the metastatic setting, in the past decade trastuzumab has become a standard component of both neoadjuvant and adjuvant treatment of most HER2? cancers, resulting in a notable reduction in disease recurrences. The Herceptin Adjuvant (HERA) randomized trial showed a significant reduction in risk of a disease-free survival event (hazard ratio [HR] 0.76) and death (0.74) at 11 years of follow-up with the receipt of 1 year of adjuvant trastuzumab compared with observation among 5,099 patients with HER2? early breast cancer. Similar results were seen in a combined analysis of data from the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trials, with significantly improved disease-free survival (HR 0.52) at 4 years among patients with operable HER2? disease treated with adjuvant trastuzumab. In the modern era, rates of LRR after the treatment of early-stage cancers continue to decline steadily, now less than 10% at 10 years. Systemic therapy has been shown to decrease LRR independent of the use of radiotherapy or type of breast surgery. However, data are limited on contemporary rates of LRR by subtype since the pivotal incorporation of trastuzumab into adjuvant treatment of HER2? disease. In this issue of the Annals of Surgical Oncology, McGuire et al. have provided LRR outcomes for 11,219 patients treated in the ‘‘trastuzumab era.’’ At a median follow-up of 53 months, the overall LRR rate was 3.4%, lowest among luminal A cancers (1.7%), intermediate among HER2? cancers (5.7%), and highest among TN cancers (7.4%). Compared with a previous systematic review published by the same group in 2012, there has been a reduction in overall LRR rates, from 7.9 to 3.4%, and this reduction in LRR is seen across all subtypes. The greatest comparative reduction occurred among HER2? patients, with LRR rates decreasing from 15.7 to 5.7%. The magnitude of this reduction should not come as a surprise and highlights the remarkable impact of targeted trastuzumab therapy among HER2? patients. The improvement seen among HER2-negative subtypes is likely attributable to concurrent ongoing improvements in imaging, pathologic evaluation, radiotherapy, and other systemic therapies. Despite an improved understanding of the behaviors of different breast cancer subtypes and an appreciable reduction in LRR as a result of targeted therapy, the nuances of individualizing treatment remain complex. McGuire et al. allude to this intricacy while raising the question of more aggressive local therapy among nonluminal breast cancers based on the yet higher LRR rates in those groups. However, Society of Surgical Oncology 2017

Diabetes insipidus uncovered during conservative management of complicated acute appendicitis

Diabetes insipidus (DI) arises from impaired function of antidiuretic hormone, characterized by hypovolemia, hypernatremia, polyuria, and polydipsia. This case is a reminder of the rare but challenging obstacle that undiagnosed DI poses in fasting surgical patients, requiring prompt recognition and vigilant management of marked homeostatic imbalances.