Adriana Bonifacino

High-resolution, handheld camera use for occult breast lesion localization plus sentinel node biopsy (SNOLL): A single-institution experience with 186 patients

BACKGROUND Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) via gamma probe and radioguided occult lesion localization (ROLL). This applies to nonpalpable invasive breast cancer or high-grade in situ carcinoma. As opposed to standard techniques, todays handheld gamma cameras enable intraoperative scintigraphic images. METHODS A cohort (N = 186) of consecutive patients with breast cancer was subjected to radioguided conservative surgery (quadrantectomy and SLN biopsy), using a standard gamma probe and a high-resolution handheld camera. Intraoperative SLN frozen section was also performed. RESULTS Neoplastic lesions were removed in 99.4% of all patients, and SLN biopsy was achieved in 99%. Of the 137 patients with invasive cancer, SLN metastasis was confirmed in 21. In 12% of patients, a second operation was required for close or tumor-positive surgical margins. DISCUSSION This combination of procedures represents an improvement in the surgical management of occult breast carcinomas and is the method of choice for accurate tumor localization and SLN biopsy. Handheld cameras have the potential to become highly useful intraoperative aids.

Cytological diagnostic features of late breast implant seromas: From reactive to anaplastic large cell lymphoma

Late breast implant seroma may be the presentation of a breast implant-associated anaplastic large cell lymphoma (BI-ALCL), which claims for a prompt recognition. However, BI-ALCL diagnosis on fine-needle aspiration (FNA) might be challenging for pathologists lacking experience with peri-implant breast effusions. Sixty-seven late breast implant seromas collected by FNA from 50 patients were evaluated by Papanicolaou smear stain and immunocytochemistry on cell blocks. A diagnostic algorithm based on the cellular composition, cell morphology and percentage of CD30+ cells was developed. Histological evaluation of the corresponding peri-prosthetic capsules was also performed. Most of the effusions (91% of the samples) were classified as reactive and 9% as BI-ALCL. In the BI-ALCL cases, medium-to-large atypical cells expressing CD30 represented more than 70% of the cellularity, whereas in in the reactive effusions CD30+ elements were extremely rare (<5%) and consisted of non-atypical elements. The reactive effusions were categorized into three patterns: i) acute infiltrate with prominent neutrophilic component (33% of the samples); ii) mixed infiltrate characterized by a variable number of neutrophils, lymphocytes and macrophages (30% of the samples); iii) chronic infiltrate composed predominantly of T lymphocytes or macrophages with only sporadic granulocytes (37% of the samples). The inflammatory cytological patterns were consistent with the histology of the corresponding capsules. Our results indicate that cytological analysis of late breast implant effusions, supported by the knowledge of the heterogeneous cytomorphological spectrum of late seromas, is a valuable approach for the early recognition of BI-ALCL.

The sexist behaviour of immune checkpoint inhibitors in cancer therapy

Background Immune checkpoint inhibitors, targeting the molecules CTLA-4, PD-1 and PD-L1, showed efficacy against several type of cancers and are currently used in clinical practice. An important biological variable that influences innate and adaptive immunity is the sex, acting through genetic, hormonal and environmental factors. The overall differences between sexes could be crucial to evaluate the response to ICIs. Materials and methods We performed a meta-analysis of Phase II-III Clinical Trials published up to June 2017 in which anti-CTLA-4, anti-PD-1 and anti-PD-L1 were studied. We extracted the OS and PFS HR differentiated by sex from subgroups analysis of each trial. We analyzed the three classes of drugs separately. Results We selected 36 Phase II-III Clinical Trials, 9 of which reported results for OS and 6 for PFS. We analyzed 2 Clinical Trials for OS with anti-CTLA-4, including 1178 patients, observing a benefit for males vs females (HR 0.65, 95% CI 0.55-0.77 vs HR 0.79, 95% CI 0.65-0.96, p 0.078). Not statistically significant results were observed with anti-PD-1 neither for OS (males vs females: HR 0.72, 95% CI 0.64-0.83 vs HR 0.81, 95% CI 0.70-0.94, p 0.285) neither for PFS (males vs females: HR 0.66, 95% CI 0.52-0.82 vs HR 0.85, 95% CI 0.66-1.09, p 0.158). We cannot perform a meta-analysis for anti-PD-L1 due to the lack of data. Conclusions Different mechanisms could be involved in sex differences with regard to immunotherapy. These differences could be relevant to identify immunological targets in order to draw studies exploring novel combinations of immunotherapy agents.

Hospitalizations in pediatric and adult patients for all cancer type in Italy: The EPIKIT study under the E.U. COHEIRS project on environment and health

Background: Cancer Registries (CRs) remain the gold standard for providing official epidemiological estimations. However, due to CRs’ partial population coverage, hospitalization records might represent a valuable tool to provide additional information on cancer occurrence and expenditures at national/regional level for research purposes. The Epidemiology of Cancer in Italy (EPIKIT) study group has been built up, within the framework of the Civic Observers for Health and Environment: Initiative of Responsibility and Sustainability (COHEIRS) project under the auspices of the Europe for Citizens Program, to assess population health indicators. Objective: To assess the burden of all cancers in Italian children and adults. Methods: We analyzed National Hospitalization Records from 2001 to 2011. Based on social security numbers (anonymously treated), we have excluded from our analyses all re-hospitalizations of the same patients (n = 1,878,109) over the entire 11-year period in order to minimize the overlap between prevalent and incident cancer cases. To be more conservative, only data concerning the last five years (2007–2011) have been taken into account for final analyses. The absolute number of hospitalizations and standardized hospitalization rates (SHR) were computed for each Italian province by sex and age-groups (0–19 and 20–49). Results: The EPIKIT database included a total of 4,113,169 first hospital admissions due to main diagnoses of all tumors. The annual average number of hospital admissions due to cancer in Italy has been computed in 2362 and 43,141 hospitalizations in pediatric patients (0–19 years old) and adults (20–49 years old), respectively. Women accounted for the majority of cancer cases in adults aged 20–49. As expected, the big city of Rome presented the highest average annual number of pediatric cancers (n = 392, SHR = 9.9), followed by Naples (n = 378; SHR = 9.9) and Milan (n = 212; SHR = 7.3). However, when we look at SHR, minor cities (i.e., Imperia, Isernia and others) presented values >10 per 100,000, with only 10 or 20 cases per year. Similar figures are shown also for young adults aged 20–49. Conclusions: In addition to SHR, the absolute number of incident cancer cases represents a crucial piece of information for planning adequate healthcare services and assessing social alarm phenomena. Our findings call for specific risk assessment programs at local level (involving CRs) to search for causal relations with environmental exposures.

FCGRs Polymorphisms and Response to Trastuzumab in Patients With HER2-Positive Breast Cancer: Far From Predictive Value?

Background The aim of the study was to validate the association between the Arg166His polymorphisms of the Fc immunoglobulin receptor 2A (FCGR2A) and the Val212Phe of FCGR3A and pathological clinical response (pCR) to trastuzumab in HER2-positive breast cancer patients. Methods Polymorphisms were characterized by pyrosequencing in 26 patients with ductal histotype breast cancer in a neoadjuvant setting and genotype association with pCR was analyzed. Results No association was found between the FCGR3A Val212Phe polymorphisms and pCR. In contrast, the FCGR2A GG genotype (Arg allele) was found to be positively associated with pCR (P = 0.012). Conclusions Our results do not support previously reported data on the effect of polymorphisms in immunoglobulin Fc receptors upon response to trastuzumab therapy.

Clinical-Pathological Features of an Occult Mixed Mucinous Male Breast Cancer: A Case Report

Mucinous carcinoma of the male breast is an uncommon malignant breast neoplasm and its diagnoses remain difficult. It is probably due to such a low rate of breast cancer cases that men tend to be diagnosed at an older age than women and with a later stage of the disease. We describe a case of a 69-year-old male who displayed a palpable lump in his right axilla several years ago, showing signs of cutaneous adnexal mucinous adenocarcinoma after biopsy. After six years and several clinical examination and systemic investigation without results, the patient underwent to fine needle aspiration cytology and subsequently a biopsy of a mass with irregular margins in the retroareolar region of his right breast. The final diagnosis was of a mixed mucinous breast cancer with neuroendocrine differentiation. The tumor cells phenotype showed Synaptophisin (+), CEA (+/-), CK-20 (-), CK-7 (+), TTF-1 (-), estrogen receptor (-), progesterone (-) and HER 2 (++). These results were unusual for a mucinous male breast carcinoma. In the presence of a lesion in the axillary area with no specific primary origin, breast cancer should never be ruled out, even in the absence of clinical evidence and with an immunohistochemical pattern not indicative of mammary origin.

Diagnostic and therapeutic path of breast cancer: effectiveness, appropriateness, and costs – results from the DOCMa study

Objective An increase in breast cancer incidence has been documented in Italy and in other countries, and some women decide by themselves to undergo diagnostic examinations outside the official screening campaigns. The aim of this paper was to analyze – in terms of effectiveness, appropriate access, and related costs – the path spontaneously followed by a sample of Italian women for the early diagnosis of breast cancer. Subjects and methods A total of 143 women who consecutively referred themselves to the breast cancer outpatient facilities at the Sant’Andrea University Hospital in Rome from May to June 2007 were enrolled in the study, gave their consent, and were screened according to their individual risk factors for breast cancer. The entire diagnostic and therapeutic path followed in the previous 2 years by each of them, either at Sant’Andrea or in other medical facilities, was reviewed and evaluated in terms of its operative efficiency and fair economic value. Results The subjects’ mean age was 47.5 years (standard deviation 13.6 years); 55% of the women were <50 years old (28% <40 years), and were thus not included in the official screening campaigns; 97 women (70%) were requesting a routine control; and 49% of them had already undergone four to seven examinations before the enrollment, although no major risk factor was present in 73.5%. After enrollment in the study, nine of the patients had surgical interventions performed on them at Sant’Andrea’s, identifying five invasive carcinomas and two ductal in situ carcinomas and two benign lesions. Operative efficiency and fair economic value were found to be optimal only in diagnostic/therapeutic paths followed at Sant’Andrea. Conclusion The diagnostic path at Sant’Andrea’s specialized center for breast cancer diagnosis and therapy is characterized by higher operative efficiency and more sustainable costs than at general hospitals, outpatient facilities run by local health authorities, or private medical centers. This result seems to confirm the present tendency to refer high-risk patients for breast cancer directly to breast units like the one at Sant’Andrea.