BACKGROUND: Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer, it may no longer be necessary either as treatment or as a guide to adjuvant treatment. The authors conducted a single-center randomized trial (INT09/98) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long-term disease control. METHODS: From June 1998 to June 2003, 565 patients aged 30 years to 65 years with T1N0 breast cancer were randomized to either quadrantectomy with (QUAD) or without (QU) axillary lymph node dissection; a total of 517 patients finally were evaluated. All patients received radiotherapy to the residual breast only. Chemotherapy for patients in the QUAD treatment arm was determined based on lymph node status, estrogen receptor status, and tumor grade. Chemotherapy for patients in the QU treatment arm was based on estrogen receptor status, tumor grade, and human epidermal growth factor receptor 2 and laminin receptor status. Overall survival (OS) was the primary endpoint. Disease-free survival (DFS) and rate and time of axillary lymph node recurrence in the QU treatment arm were the secondary endpoints. RESULTS: After a median follow-up of >10 years, the estimated adjusted hazards ratio of the QUAD versus QU treatment arms for OS was 1.09 (95% confidence interval, 0.59-2.00; P 5.783) and was 1.04 (95% confidence interval, 0.56-1.94; P 5.898) for DFS. Of the 245 patients in the QU treatment arm, 22 (9.0%) experienced axillary lymph node recurrence. The median time to axillary lymph node recurrence from breast surgery was 30.0 months (interquartile range, 24.2 months-73.4 months). CONCLUSIONS: Patients with T1N0 breast cancer did not appear to benefit in terms of DFS and OS from immediate axillary lymph node dissection in the current randomized trial. The biological characteristics of the primary tumor appear adequate for guiding adjuvant treatment. Cancer 2014;120:885-93.

BackgroundAndrogen receptors (AR) are frequently expressed in breast cancers, but their implication in cancer growth is still controversial. In the present study, we further investigated the role of the androgen/AR pathway in breast cancer development.MethodsAR expression was evaluated by immunochemistry in a cohort of 528 postmenopausal breast cancer patients previously examined for the association of serum testosterone levels with patient and tumor characteristics. AR expression was classified according to the percentage of stained cells: AR-absent (0%) and AR-poorly (1%-30%), AR-moderately (>30%-60%), and AR-highly (>60%) positive.ResultsStatistical analysis was performed in 451 patients who experienced natural menopause. AR-high expression was significantly related with low histologic grade and estrogen receptor (ER)- and progesterone receptor (PR)-positive status (P trend<0.001). Mean testosterone levels were significantly higher in the AR-high category than in the other categories combined (P=0.022), although a trend across the AR expression categories was not present. When women defined by ER status were analyzed separately, regression analysis in the ER-positive group showed a significant association of high testosterone levels with AR-highly-positive expression (OR 1.86; 95% CI, 1.10-3.16), but the association was essentially due to patients greater than or equal to 65 years (OR 2.42; 95% CI, 1.22-4.82). In ER-positive group, elevated testosterone levels appeared also associated with AR-absent expression, although the small number of patients in this category limited the appearance of significant effects (OR 1.92; 95% CI, 0.73–5.02): the association was present in both age groups (<65 and ≥65 years). In the ER-negative group, elevated testosterone levels were found associated (borderline significance) with AR-absent expression (OR 2.82, 95% CI, 0.98-8.06). In this ER-negative/AR-absent subset of tumors, elevated testosterone levels cannot stimulate cancer growth either directly or after conversion into estrogens, but they probably induce increased synthesis of some other substance that is responsible for cancer growth through binding to its specific receptor.ConclusionsThe findings in the present study confirm that testosterone levels are a marker of hormone-dependent breast cancer and suggest that the contemporary evaluation of ER status, AR expression, and circulating testosterone levels may identify different subsets of cancers whose growth may be influenced by androgens.

The aim of this retrospective study was to analyze the incidence of further nonsentinel node metastases at completion lymphadenectomy of the groin after a positive sentinel node biopsy to evaluate whether radical dissection remains the treatment of choice for these patients. Patients treated at the National Cancer Institute of Milan between January 1999 and December 2006 were reviewed retrospectively. The analysis included patients with a diagnosis of positive sentinel node biopsy of the groin (clinically negative) who underwent completion groin, iliac, and obturatory dissections. The primary melanoma was located on the lower extremities and trunk in 82.5 and 17.5%, respectively. The median follow-up was more than 30 months. The number of positive sentinel nodes was considered, as well as the size and location of the metastases (micro vs. macro). After radical dissection, the number and the location (groin, iliac, or groin+iliac nodes) of further nonsentinel node metastases were analyzed. The frequency of further nonsentinel node metastases at completion of groin dissection was correlated to Breslow's thickness and to the characteristics of the positive sentinel node biopsy. A total of 1581 patients with primary melanoma (>1 mm, or Clark's IV-V) underwent lymphatic mapping and sentinel node biopsy: 752 patients had sentinel node biopsy at the groin basin; among these, 150 (20%) patients presented positive sentinel node biopsy and underwent completion radical dissection (groin, obturatory, and external iliac+obturatory radical node dissections). We found further positive nonsentinel node metastases in 36 of 150 (24%) patients, 69% (25 of 36) of which were located in the iliac-obturator area and 31% in the groin area only: 16 patients (44.4%) had one additional metastatic node and seven patients (19.4%) had two, whereas 13 (36.1%) had three or more. In 22 cases (61.1%), the sentinel node showed a macrometastasis (>2 mm deposit in the node) and in 14 cases (38.9%) a micrometastasis (<2 mm deposit). In conclusion, there is clear evidence that patients with a positive sentinel node biopsy could have further positive nonsentinel node metastases (in our series, 24%). Although it is well known that the impact of sentinel node biopsy on survival of melanoma patients has yet to be defined, to obtain a clear nodal basin and regional control a groin+iliac-obturatory radical node dissection remains an appropriate procedure in the presence of a positive sentinel node biopsy at the groin level. This could be considered a standard treatment until new data, provided by ongoing studies, indicate new parameters for selecting patients for completion lymph node dissection.

A fundamental question in surgery of only magnetic resonance imaging (MRI)-detected breast lesions is to ensure their removal when they are not palpable by clinical examination and surgical exploration. This is especially relevant in the case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine patients were enrolled in the study, 21 patients with breast lesions detected by both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI findings only. Preoperative bMRI allowed staging the disease and localizing the lesion. In the operating theater, contrast medium was injected 1 minute before skin incision. After removal, surgical specimens were submitted to ex vivo MRI, performed using a dedicated surface coil and Spair inversion recovery sequences for suppression of fat signal intensity. All MRI enhancing lesions were completely included within the surgical specimen and visualized by ex vivo MRI. In the first 21 patients, bMRI was able to visualize branching margins or satellite nodules around the core lesion, and allowed for better staging of the surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12 malignant tumors, otherwise undetectable, that were all visualized by ex vivo MRI. This is the first description of a procedure that re-enhances breast lesions within a surgical specimen, demonstrating the surgical removal of nonpalpable breast lesions diagnosed only with bMRI. This new strategy reproduces the morphology and the entire extension of the primary lesion on the specimen, with potentially better local surgical control, reducing additional unplanned surgery.

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