Primary tumor location predicts the site of local relapse after nipple-areola complex (NAC) sparing mastectomy.

PURPOSE: To assess the oncological safety of nipple-areola complex (NAC) sparing mastectomy in breast cancer patients. METHODS: From 2010 to 2015, 518 breast cancer patients were submitted to NAC sparing mastectomy. Breast MRI and intraoperative assessment of the subareolar (SD) and proximal (ND) nipple ducts were performed to predict NAC involvement. Significant associations between pre- and postoperative variables with SD/ND involvement and with the risk of local recurrence were retrospectively investigated. RESULTS: SD/ND were involved in 26.1% of the cases. Final pathology of SD/ND was predicted by tumor-NAC distance at MRI and intraoperative pathology with 75 and 93% accuracy, respectively. NAC involvement was more frequent in case of positive ND than positive SD (68.3 vs. 38.3%; p = 0.003). Fourteen (2.7%) local relapses developed over a mean follow-up of 33 months. Ki-67 ≥25% (p = 0.002) and high tumor grade (p = 0.027) correlated with local recurrence. Most relapses developed in the subcutaneous tissue of the quadrant where the primary tumor was located (12/14; 85.7%). No local relapses occurred in patients who received post-mastectomy radiotherapy as compared to patients who did not, although they had a higher rate of positive surgical margins (40.5 vs. 16.2%; p = 0.000). CONCLUSIONS: NAC involvement can be predicted by MRI and intraoperative pathology of ND/SD. Local recurrences after NAC sparing mastectomy almost invariably develop in the same quadrant where the primary tumor was located and in highly proliferative tumors.

Omission of axillary dissection after a positive sentinel node dissection may influence adjuvant chemotherapy indications in operable breast cancer patients.

BACKGROUND: This study was designed to evaluate how the omission of axillary dissection would have altered the indication for adjuvant chemotherapy (ACT) in patients with early breast cancer submitted to conservative surgery with one or two positive sentinel lymph nodes (SLNs). METHODS: We identified 321 women in our institutional database who fulfilled the characteristics. All underwent completion axillary lymph node dissection (AD). Each case was blindly reviewed by our breast team in two rounds, and the total number of positive lymph nodes was disclosed only in the second. At each round, the panel chose between: (1) recommend, (2) discuss, (3) do not recommend ACT. Changes between round 1 and 2 were studied by the marginal homogeneity test. Exploratory logistic regression analyses were performed to study predictors of non-SLN involvement and of changes in the indication for ACT. RESULTS: AD revealed non-SLNs metastases in 96 patients (30 %). Fifty-two patients (16 %) had their initial indication changed at round 2 (p < 0.001). Most of the changes were toward ACT (83 %), and all except two occurred in patients with immunohistochemically defined luminal A and luminal B/HER2-negative tumors. In these two subgroups, a Ki67 above the median value (21 %) was the only independent predictor of no change in the indication to ACT at round 2. CONCLUSIONS: Omission of AD in patients with one or two positive SLNs may change the indication to ACT in a significant proportion of patients with hormone receptor-positive/HER2-negative tumors. All implications should be taken into account before abandoning AD, including a possible biologically tailored surgical approach.

Reoperation rate after breast conserving surgery as quality indicator in breast cancer treatment: A reappraisal.

AIM: To analyse the role of repeated breast surgery (RBS) after breast conserving surgery (BCS) as a quality indicator in a consecutive series of breast cancer patients. METHODS: Data from 1233 breast cancer patients submitted to BCS from 2015 to 2019 were reviewed. The influence of several variables on RBS rate (182/1232; 14.8%) was examined. Univariate and multivariate analyses were conducted to look for significant associations with the risk of RBS. RESULTS: Surgical workload, BCS rate and clinicopathological variables were consistent over the study period, while RBS rate decreased after the introduction of shaving of cavity margins (from 17.9% to 9.5%). Tumor persistence at RBS was higher for mastectomy vs. re-excision (87.3% vs. 37.8%; p = 0.05), inconclusive vs. positive diagnostic biopsy (48.2% vs. 69.4%; p = 0.003), ductal carcinoma in situ vs. invasive carcinoma (69.0% vs. 51.3%; p = 0.046) and lower after neoadjuvant therapy (14.3% vs. 57.8%; p = 0.044). Several clinicopathological variables were associated with the risk of RBS, but only multifocality [Odds Ratio (OR): 1.8; p = 0.009], microcalcifications (OR: 2.0, p = 0.000), neoadjuvant therapy (OR: 0.4; p = 0.014), pathological intraoperative assessment (OR: 0.6; p = 0.010) and shaving of cavity margins (OR: 0.3; p = 0.000) retained independent value at multivariate analysis. CONCLUSIONS: RBS rate can be reduced by shaving of cavity margins. Current standards for RBS should not be made more stringent due to the existence of non-actionable risk factors. The value of RBS as a quality indicator should be scrutinzed.

Pathological classification of ductal carcinoma in situ of the breast correlates with surgical treatment and may be predicted by mammography.

In order to assess the correlation of pathological and radiological features of ductal carcinoma in situ (DCIS) of the breast and their association with surgical outcome, a consecutive series of 150 patients was retrospectively examined. Pathological slides from all patients were divided into three categories according to the pathological EPWG (European Pathologist Working Group) and DIN (Ductal Intraepithelial Neoplasia) classifications, which showed very good inter-correlation (r=0.99) (whole series). Mammographic images from 46 of these cases were blindly classified into five categories according to the level of radiological suspicion (R), morphology of calcifications (Ca) and preoperative results of needle biopsy (C/B) (limited series). No significant differences in the distribution of clinical and pathological variables were detected among whole and limited series. The lesions were grouped into two (low versus high) pathological (PRG), radiological (RRG and CaRG) and needle biopsy (C/BRG) risk groups. PRG was associated with both RRG (p=0.002) and CaRG (p=0000), but not with C/BRG. Correlations with surgical outcome were also explored, with lesions of high PRG being more likely to undergo re-excision for inadequate first wide local excision [odds ratio (OR)=2.1], mastectomy (OR=2.6) and nodal staging procedures (OR=3.8) in the whole series. Conversely, no significant correlation was found between PRG, RRG, CaRG and C/BRG with surgical outcome in the limited series. We suggest that pathological features of DCIS are associated with surgical outcome and may be predicted by mammography.

Attitudes of Italian gynaecologists towards prophylactic oophorectomy at hysterectomy for non-malignant conditions.

OBJECTIVE: To compare the attitudes of Italian oncologic gynaecologists towards prophylactic oophorectomy at hysterectomy for a non-neoplastic reason. STUDY DESIGN: A four-item two-part questionnaire was submitted to 170 gynaecologists attending a national conference on gynaecologic oncology. RESULTS: About 92% of gynaecologists reported they would perform prophylactic oophorectomy in women over 50 years, but only 14% said they would in patients aged 45-50; a family history of cancer emerged as a major decision-making criterion for performing oophorectomy in the younger set of patients. CONCLUSION: Our brief survey confirms the wide variability in attitudes among gynaecologists towards performing prophylactic oophorectomy at hysterectomy for a non-neoplastic pathology in women aged 40-50.

Differences in prognostic molecular markers between women over and under 45 years of age with advanced ovarian cancer.

PURPOSE: The purpose of this study was to determine whether differences in molecular markers might explain the better prognosis of women < or =45 years of age versus women >45 years of age diagnosed with ovarian cancers. EXPERIMENTAL DESIGN: Tissue sections from women with stage III-IV ovarian cancers were examined for expression of CD34, p53, and HER2. The Kaplan-Meier method and Cox Proportional Hazard analyses were used to identify predictors for outcome. RESULTS: Fifty-two women < or =45 years of age were matched with 52 women who were >45 years old. Of the 46 available tissue sections, 24 were from the younger age group (mean age, 41 years), and 22 were from the older age group (mean age, 61 years). Based on CD34 expression, tumors from women >45 years of age had lower microvessel density (MVD) compared with tumors of younger women (10.3 versus 16.1 microvessels per x400 field; P = 0.03). Lower MVD (< or =11 microvessels per x400 field) predicted for a worse prognosis than higher MVD (>11 microvessels per x400 field) in the overall study group (P = 0.001) and within the older subgroup (P = 0.03). The expressions of p53 (P = 0.13) and HER2 (P = 0.49) did not vary between the two age groups. The median survivals of those with tumors that overexpressed p53 and HER2 were 28.6 and 23.9 months compared with 51.7 and 38.6 months in those with cancers that underexpressed these markers, respectively (P = 0.09 for p53, P = 0.15 for HER2). CONCLUSIONS: Ovarian cancers in women >45 years of age had lower MVD compared with those in women < or =45 years of age. Lower MVD was an independent prognostic factor for decreased survival. Lower frequency of neovascularization in these cancers may contribute to the decreased survival observed in women >45 years of age.

MRI and intraoperative pathology to predict nipple-areola complex (NAC) involvement in patients undergoing NAC-sparing mastectomy.

BACKGROUND: Nipple-areola sparing mastectomy (NSM) with immediate implant reconstruction is an option for patients with non-locally advanced breast cancer. The prediction of occult tumour involvement of the nipple-areola complex (NAC) may help select candidates to NSM. PATIENTS AND METHODS: We prospectively recorded clinical and pathological data, magnetic resonance imaging (MRI) results and intraoperative pathological assessments of the subareolar (SD) and proximal nipple ducts (ND) of 112 consecutive breast cancer patients scheduled for NSM. All parameters were correlated with final pathological NAC assessment by univariate and multivariate analysis. RESULTS: Thirty-one patients (27.7%) had tumour involvement of the NAC. At univariate analysis, age (p=0.001), post-menopausal status (0.003), tumour central location (p=0.03), tumour-NAC distance measured by MRI (p=0.000) and intraoperative pathologic assessment (SD+ND) (p=0.000) were significantly correlated with NAC involvement. At multivariate analysis, only MRI tumour-NAC distance (p=0.008) and menopausal status (p=0.039) among all preoperative variables retained statistical significance. The sensitivity and specificity of MRI tumour-NAC distance were 32.2% and 88.6% and those of intraoperative pathologic assessment were 46.7% and 100%, respectively. Sensitivity, specificity and accuracy of the double assessment (MRI plus intraoperative pathology) were 50.0%, 96.2% and 84.1%, respectively. CONCLUSION: Intraoperative pathologic assessment and tumour-NAC distance measured by MRI are the most important predictors of occult NAC involvement in breast cancer patients. A negative pathological assessment and a tumour-NAC distance ⩾ 5 mm allow optimal discrimination between NAC positive and NAC negative cases and may serve as a guide for the optimal planning of oncological and reconstructive surgery.

Nipple-areola complex sparing mastectomy with periareolar pexy for breast cancer patients with moderately ptotic breasts.

BACKGROUND: Nipple-areola complex sparing mastectomy (NSM) with immediate implant reconstruction has been recently introduced for breast cancer patients who are not candidates for breast preserving surgery. As the cosmetic results in moderately ptotic breasts may not be optimal, a modified NSM with a periareolar pexy (PP-NSM) was introduced at our Institution. Patients selection criteria and complication rates of PP-NSM were prospectively recorded and compared with those of the classical NSM. RESULTS: Over a period of 11 months, 22 PP-NSMs and 35 NSMs were performed. The mean jugular-nipple distance was significantly longer in the PP-NSM as compared with the NSM (22.6 vs. 19.6 cm; p=0.000), whereas the mean inframammary fold-areola distance was superimposable (5.4 cm). The periareolar mastopexy led to a mean cranial transposition of the nipple-areola complex (NAC) of 2.2 cm (range 1.5-4 cm). Mean breast weight was significantly higher in the PP-NSM as compared with the NSM cohort (336 vs. 236 g; p=0.003). The only case of total NAC necrosis occurred in the PP-NSM group. Partial NAC necrosis was slightly more frequent in the PP-NSM than in the NSM group (13.6% vs. 2.9%%; p=n.s.), possibly due to the higher percentage of smokers (41.0% vs. 14.0%; p=0.05). Early cosmetic results were good to excellent from the surgeon's and the patient's point of view in over 80% of the cases. CONCLUSIONS: PP-NSM allows good cosmetic results and low complication rates in patients with moderately ptotic breasts requiring a mastectomy. In particular, PP-NSM seems to be a good option for women at high risk for developing breast cancer and for selected patients affected by non-locally advanced breast cancer.

Comparison of two models for the prediction of nonsentinel node metastases in breast cancer.

BACKGROUND: It is debated whether all patients with a positive sentinel node dissection (SLND) should be submitted to axillary lymph node dissection (ALND). Models have been developed to estimate the likelihood of nonsentinel node (non-SLN) metastases. METHODS: The accuracy of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and MD Anderson scoring system for the prediction of non-SLN status was tested in a consecutive series of 186 SLN-positive breast cancer patients. A multivariate analysis was performed to assess which parameters independently predicted the presence of non-SLN metastases. RESULTS: The predictive accuracy of the MSKCC nomogram measured by the receiver operating characteristic curve was 0.71, and it was best in patients with <10% risk of non-SLN metastases (sensitivity 100% and specificity 96%). The MD Anderson score predicted non-SLN involvement with low accuracy because it classified 85% of the patients in the intermediate-risk groups. Only SLN macrometastases and tumor multifocality independently predicted non-SLNs involvement. CONCLUSIONS: The MSKCC nomogram can help individualize the surgical treatment of SLN-positive breast cancer when the likelihood of further axillary involvement is low or surgical risks are higher.

Mast cell density, angiogenesis, blood clotting, and prognosis in women with advanced ovarian cancer.

OBJECTIVE: To determine clinical or biological associations between mast cell density, blood clotting, angiogenesis, and survival of patients with advanced ovarian cancer. METHODS: Tumor tissue sections were assessed for mast cell density by staining for mast cell tryptase, blood clotting by staining of thrombosed blood vessels, and angiogenesis by CD34 expression. Chi-square, Kaplan-Meier, and Cox proportional hazard statistical analyses were used. RESULTS: 44 women with stage III-IV ovarian cancers had tumor blocks available for immunohistochemical analysis. Higher mean vessel density (MVD) (>11 vessels/400x field) predicted for better survival than lower MVD (< or =11 vessels/400x field) (P = 0.004). Women whose tumors had low levels of peri-tumoral mast cell infiltration had a mean survival of 40.6 months compared to 50.6 months in those whose tumors had high levels (P = 0.47). Tumors with higher MVD and high peri-tumoral mast cell infiltration had a mean survival of 80.3 months compared to 37.8 months in those with low mast cell density or low MVD (P = 0.015). Patients with tumors showing a low degree of blood clotting had a mean survival of 45.5 compared to 45.1 months in those with tumors showing a high degree of blood clotting (P = 0.91). There was no significant association between angiogenesis and mast cell density (P = 0.123). In multivariate analysis, higher MVD remained as a significant prognostic factor for improved survival after adjusting for clotting and mast cell density. CONCLUSIONS: Our data suggest that peri-tumoral mast cell infiltration in tumors with high MVD predicts for improved survival in women with advanced epithelial ovarian cancer.

Clinicopathologic features of six cases of primary cervical lymphoma.

OBJECTIVE: Primary lymphoma of the uterine cervix is rare, with less than 60 cases reported. We present a series of 6 patients with cervical lymphoma and review the literature. STUDY DESIGN: Between 1988 and 2003, we identified 6 women with primary lymphoma of the uterine cervix treated at our institutions. Data for analysis were obtained from hospital charts, office records, and tumor registry files. We also reviewed 20 published reports on cervical lymphoma, providing information on 58 additional patients. RESULTS: The median age at diagnosis was 52 years (range 40-76). Three patients had an abnormal Papanicolaou test within 6 months of the diagnosis. Mean tumor size was 8.3 cm (range 3-14 cm). On the basis of the Ann Arbor system of staging where "E" denotes extranodal tumor origin, 2 patients had stage IE, 1 had stage IIIE, and 3 had stage IVE disease. The median follow-up for these 6 women was 33 months (range 12-120). Adding the 6 patients in our series to the 58 patients obtained from published reports, 43 had stage IE, 14 had stage IIE, 2 had stage IIIE, and 5 had stage IVE disease. There was no consistent pattern of treatment identified from our literature review. CONCLUSION: Primary lymphoma of the uterine cervix is a rare malignancy. Most patients present with stage IE disease. Women with localized disease typically respond to various combinations of surgery, chemotherapy, and radiotherapy. Combination chemotherapy with tailored radiotherapy appears to be the preferred treatment option in women with advanced disease.

Radical hysterectomy followed by tailored postoperative therapy in the treatment of stage IB2 cervical cancer: feasibility and indications for adjuvant therapy.

OBJECTIVE: To determine the outcome, complications and likelihood of requiring adjuvant therapy of patients with stage IB2 cervical cancer treated with primary radical hysterectomy and lymph node dissection. METHODS: Clinical and pathologic data between 1985 and 1999 were reviewed. Associations between clinical and pathologic variables were tested using the Fisher's exact test. Survival was estimated using the Kaplan-Meier method with significance being calculated using the Log Rank test. RESULTS: Six hundred radical hysterectomies were performed during the study period. Fifty-eight of these women (9.6% of all radical hysterectomies) were diagnosed with FIGO stage IB2 cancers. Sixteen patients (28%) had positive pelvic lymph nodes. Forty-six patients (79%) had invasion involving the outer 1/3 of the cervical stroma, six had positive vaginal margins while five had occult parametrial extension. After retrospective review of the histopathologic data from this case series, criteria from two recently published prospective multicenter Gynecologic Oncology Group (GOG) trials were applied to this data set. According to criteria established by GOG protocol 92, 30 (52%) patients should have theoretically received adjuvant pelvic radiation while 21 (36%) would have qualified for adjuvant chemotherapy and radiation according to the results of GOG protocol 109. In actual fact, only 35 patients (60%) received adjuvant radiotherapy and one received adjuvant chemo-radiation. Severe toxicity was unusual with two developing urinary fistulae and one having a pulmonary embolism. Despite the lack of adjuvant therapy in most cases, only 21 women (38%) recurred of whom 11 failed on the pelvic wall, with an estimated 5-year survival of 62.1%. CONCLUSIONS: Radical hysterectomy and tailored adjuvant radiation therapy in stage IB2 cervical cancer is feasible. Even without the liberal use of adjuvant therapy, survival in this high-risk group compares favorably to primary chemotherapy and radiation. According to recently published randomized clinical trials, most patients should receive adjuvant postoperative therapy. The benefits of this multimodality approach require randomized study.