The Proper Ki-67 Cut-Off in Hormone Responsive Breast Cancer. A Monoinstitutional Analysis with Long-Term Follow-Up

Introduction: Breast cancer is a heterogeneous disease. Our study focuses on a monoinstitutional series of patients affected by Hormone Responsive carcinomas (luminal A and luminal B) and aims to define an optimal Ki-67 cut-off, to correctly stratify these patients into risk classes, using the ImmunoHistoChemical (IHC) surrogates of the Molecular Subtypes, according to the St. Gallen guidelines. Methods: We analyzed 1685 patients. These patients underwent both radical and conservative surgeries with Sentinel Lymph Node Biopsy eventually followed by Axillary Dissection (AD). Furthermore, all the patients underwent adjuvant therapies according to the guidelines. A retrospective univariate analysis was performed and survival curves (Disease-Related Survival, DRS, and Disease-Free Survival, DFS) were carried out according to the following ki-67 risk classes: Low Risk (Ki-67 ≤ 14%); Intermediate Risk (Ki-67 15% ÷ 20%); High Risk (Ki-67 > 20%). Results: 14 yy DRS was 98% in LA and 85% in LB with a ki-67 cut-off of 14% (p=0.037) vs 95% (LA) and 83% (LB) with a ki-67 cut-off of 20% (p=0.003). 14yy DFS was 85% in LA and 72% in LB with a ki-67 cut-off of 14% (p=0.017) vs 83% (LA) and 66% (LB) with a ki-67 cut-off of 20% (p<0.000). Discussion: Our results confirmed that the 20% Ki-67 cut-off is more reliable in differentiating patients at low or high risk of recurrence and death, and stratifying patients eligible for adjuvant chemotherapy. Thus, despite its poor reproducibility, the identification of the most accurate ki-67 index assumes a pivotal relevance in guiding a tailored strategy among patients with this specific profile of breast cancer, as well as the molecular surrogates, in order to avoid harmful overtreatments

Importance of perforating vessels in nipple-sparing mastectomy. an anatomical description

BACKGROUND: Nipple-sparing mastectomy (NSM), understood as an oncologically valid procedure, is relatively new, and is an evolution of traditional mastectomy, particularly in relation to breast-conserving surgery. The anterior perforating branches are responsible for the cutaneous vascularization of the breast skin, and their preservation is a fundamental step to avoid possible postoperative necrosis. Therefore, evaluating the potential complications of cancer-related reconstructive surgical procedures such as NSM, both the distance of the tumoral lesion from the skin and the surgical incision site should be carefully considered. The preferred site of incision corresponds to the inframammary fold or possibly the periareolar area. METHODS: We retrospectively reviewed 113 patients who underwent NSM from January 2005 to October 2012 to evaluate skin complications. The anatomical study was performed by magnetic resonance imaging of the breast. RESULTS: Only one of the 113 women who had undergone a NSM procedure had total necrosis (0.9%) and six patients had partial necrosis (5.8%) of the nipple-areola complex

Contralateral prophylactic mastectomies. Correlations between primary tumor and histological findings of controlateral breast

Backgound: In Italy in 2015 48,000 new cases of breast carcinomas were diagnosed. Women who are diagnosed with breast cancer have a significant risk of developing contralateral breast cancer during the rest of their lives and this risk is closely associated to the family history, to the onset of breast cancer at a young age and is expressed at about 0.5 to 1% of metachronous tumors per year. The purpose of this work was to evaluate which and how many neoplastic lesions were seen in the contralateral breast that underwent prophylactic mastectomy and to understand what factors predict the appearance of such lesions. Methods: 168 bilateral mastectomies were analyzed in patients with an average age of 47 years, carried out from July 2008 to April 2016, at the Breast Unit of the Sant’Andrea Hospital. We considered women of any age suffering from unilateral breast cancer without either clinical or radiological evidence of a malignant lesion in the contralateral breast and negative for mutations of the BRCA1-BRCA2 genes test. Of the 168 bilateral mastectomies 35 patients were excluded from the study because they underwent neoadjuvant chemotherapy, another 35 patients because they were suffering from a bilateral neoplasia and 7 cases because they had mutated BRCA1 or BRCA2 genes. Therefore the remaining 91 patients were included in the study. Results: Both the histological features of the primary tumor and any lesions found in the contralateral prophylactic breast were analyzed. Histological examination of the main breast showed 59 cases of Invasive Ductal Carcinoma (IDC), 17 cases of Invasive Lobular Carcinoma (ILC), 9 cases of In Situ Ductal Carcinoma (ISDC), 3 microinvasive ductal, 1 invasive tubular carcinoma, 1 in situ lobular and 1 widespread in situ. In the contralateral breast, the definitive histological examination revealed that 47 patients had an occult lesion in the prophylactic contralateral breast; in particular 2 cases of LIN 1, 7 cases of LIN2, 6 cases of lobular carcinoma in situ, 26 between DIN1A/DIN1A-B/DIN1B, 4 cases of carcinoma in situ and 2 cases of Invasive Ductal Carcinoma. The correlation obtained from the observation of the main tumor has shown that in a total of 59 invasive ductal carcinoma 32 have a controlateral occult lesions and in a total of 17 cases of invasive lobular carcinoma 9 have an occult lesion in the prophylactic breast. Of these lesions, the multicentric relationship is that 50% of invasive ductal and invasive lobular carcinoma of the main breast have a contralateral lesion. Conclusion: In conclusion we would like to remind, as demonstrated by our follow-up data and as the literature reiterates, that this surgery does not improve patient survival. Certainly patients with unilateral breast cancer have many surgical therapies to be able to deal with not only having a bilateral mastectomy. The end point of this work is try to understand the risk factors of having a contralateral breast lesion to reduce the probability of a metachronous cance

Carcinoma sieroso papillare del peritoneo in paziente già operata di carcinoma mammario. Caso clinico

Il carcinoma sieroso papillare del peritoneo (PPSC) è un tumore raro che si riscontra più frequentemente nel sesso femminile. L?età media al momento della diagnosi è di 56 anni. Si diffonde coinvolgendo il peritoneo, la superficie delle ovaie e la pelvi. L?istologia è indistinguibile dall?analogo tumore ovarico, cioè il carcinoma sieroso papillare (PSCO). L?istogenesi del PPSC è probabilmente correlata all?epitelio celomatico embrionale. Sintomi e segni clinici tipici sono distensione addominale, costipazione, nausea, vomito, riduzione dell?appetito, malessere generale e perdita di peso. La chirurgia citoriduttiva, in aggiunta alla chemioterapia con cisplatino e ad altre terapie come l?immunoterapia e la radioterapia, aumenta la sopravvivenza dei pazienti affetti da PPSC. Viene descritto il caso di una paziente di 51 anni, già operata di carcinoma mammario, nella quale si manifestavano alcuni dei segni e sintomi descritti. L?intervento chirurgico dimostrò le localizzazioni sierose caratteristiche. Si fece una larga exeresi ma la malata morì 14 mesi dopo per la fatale progressione della malattia. English version The peritoneal papillary serous carcinoma (PPSC) is a rare tumor more frequently revealed in female. The onset mean age is 56 years. It implicate peritoneum, ovary?s surface and pelvis. The histology of this disease is similar to papillary serous carcinoma ovary (PSCO). The PPSC histogenesis is probably correlated to coelomatic embryonal epithelium. Clinical characteristics are abdominal swelling, constipation, nausea, emesis, inappetence, feel unwell, lose weight. The cytoreductive surgery and the cisplatinum chemotherapy, and other treatments like immunotherapy and radiotherapy, increase the PSCP patient survival. A case of a 51 years old patient with previous surgery for breast cancer is here described. She show some of the yet described clinical findings. At the surgery we found the typically serous peritoneal localizations. We performed a debulking, and the patient died 14 months after the operation due to the disease progression

The Breast-Q assessment: Sant'Andrea experience

Despite in the last 20 years breast surgery has become less mutilating, mastectomy is indicated in approximately 30% of cases, not only for large invasive carcinoma, but also for multicentric tumors and intraductal diffuse carcinomas. The nipple loss is experienced by the patients like a mutilation; we achieved a significant improvement of the aesthetic result performing Nipplesparing mastectomy (NSM), joined with reconstruction techniques. This approach has a positive impact on psychology and quality of life (QOL) of breast cancer patients. To evaluate these important aspects, we retrospectively applied the BREAST-Q questioner to 101 patients underwent a NSM. BREAST-Q is an instrument designed by the Evelyn H. Lauder Breast Center, MSKCC (NY), to assess outcomes among women undergoing different types of breast surgery: we chose reconstruction module that is comprised of two domains: patient satisfaction and QOL. There are six subthemes (physical, psychosocial and sexual well-being patient, satisfaction with breast, satisfaction with overall outcomes and satisfaction with care). From December 2003 to September 2013 we performed 157 NSMs with immediate breast reconstruction on a court of 117 patients. Selection criteria included women with preoperative diagnosis of breast cancer, tumor at least 1 cm from nipple- areola complex (NAC) without nipple discharge or NAC retraction. The median follow-up was 40 months with an age range between 19 and 72 y. We recorded 2 deaths for breast cancer, with a overall survival of 97% and a rate of local recurrence of 8.5% (10 cases). Our follow-up program included medical interview, examination of routine clinical and imaging findings, and collecting information by the BREAST-Q survey. 101 patients agreed the questioner. Our results confirm that BREAST-Q is an useful to evaluate QOL and obtain a more tailored surgery. Patients are very interested to a chance of explaining their point of view or suggesting improvements or propose grievances to the surgical equipe. This is a preliminary report, even if findings are tell now encouraging: the definitive results need greater casemix and longer follow-up. We are already satisfied about the contribution of our Breast Unit.Despite in the last 20 years breast surgery has become less mutilating, mastectomy is indicated in approximately 30% of cases, not only for large invasive carcinoma, but also for multicentric tumors and intraductal diffuse carcinomas. The nipple loss is experienced by the patients like a mutilation; we achieved a significant improvement of the aesthetic result performing Nipplesparing mastectomy (NSM), joined with reconstruction techniques. This approach has a positive impact on psychology and quality of life (QOL) of breast cancer patients. To evaluate these important aspects, we retrospectively applied the BREAST-Q questioner to 101 patients underwent a NSM. BREAST-Q is an instrument designed by the Evelyn H. Lauder Breast Center, MSKCC (NY), to assess outcomes among women undergoing different types of breast surgery: we chose reconstruction module that is comprised of two domains: patient satisfaction and QOL. There are six subthemes (physical, psychosocial and sexual well-being patient, satisfaction with breast, satisfaction with overall outcomes and satisfaction with care). From December 2003 to September 2013 we performed 157 NSMs with immediate breast reconstruction on a court of 117 patients. Selection criteria included women with preoperative diagnosis of breast cancer, tumor at least 1 cm from nipple- areola complex (NAC) without nipple discharge or NAC retraction. The median follow-up was 40 months with an age range between 19 and 72 y. We recorded 2 deaths for breast cancer, with a overall survival of 97% and a rate of local recurrence of 8.5% (10 cases). Our follow-up program included medical interview, examination of routine clinical and imaging findings, and collecting information by the BREAST-Q survey. 101 patients agreed the questioner. Our results confirm that BREAST-Q is an useful to evaluate QOL and obtain a more tailored surgery. Patients are very interested to a chance of explaining their point of view or suggesting improvements or propose grievances to the surgical equipe. This is a preliminary report, even if findings are tell now encouraging: the definitive results need greater casemix and longer follow-up. We are already satisfied about the contribution of our Breast Unit

Beyond BRCA1 and BRCA2: deleterious variants in DNA repair pathway genes in italian families with breast/ovarian and pancreatic cancers

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches

Minimally invasive access to the axilla

Ed. Springe

“Utilizzo di una nuova forbice ad ultrasuoni nella linfoadenectomia ascellare. Risultati preliminari”

Minerva Chirurgica Vol. 63 Supll.1, N. 3, pgg 158-6