Furio Maggiorotto

Menopause after breast cancer: a survey on breast cancer survivors

UNLABELLED Due to the younger age and the ever wider use of adjuvant chemotherapy and antiestrogens, menopausal symptoms are a frequent cause of concern for breast cancer patients. OBJECTIVES To determine the prevalence of menopausal symptoms, and to explore the attitudes toward Hormone Replacement Therapy (HRT) or other treatments and the willingness to take oestrogen in breast cancer patients. METHODS A questionnaire-based survey on 250 breast cancer patients treated and followed-up at our department. Of them 144 (Group A) were in postmenopause and 106 (Group B) were in premenopause at time of diagnosis. RESULTS Adjuvant therapy with tamoxifen or tamoxifen plus chemotherapy is associated with a significant worsening of menopause-related symptoms of women belonging to Group A. These women are more concerned about risk of breast cancer recurrence than about risk of osteoporosis (P=0.05) and heart disease (P=0.006). Seventy-eight percent are against the use of HRT; only 22% would consider taking HRT mainly for vasomotor symptoms relief and osteoporosis prevention. The incidence of vasomotor and dystrophic symptoms is significantly higher in women belonging to Group B treated with chemotherapy and/or hormonotherapy as compared with postmenopausal women (P<0.000 and P=0.02, respectively). Premenopausal women are more concerned about risk of breast cancer recurrence than older women (P=0.09) and at the same time are significantly more worried about the impairment of the quality of life due to adjuvant therapy (P=0.005). Younger women are more prone to consider HRT than postmenopausal women (P=0.05). Sixty-six percent are against HRT use, and 34% would consider taking HRT to alleviate vasomotor and dystrophic symptoms and to prevent osteoporosis. CONCLUSIONS Breast cancer survivors are interested to treatments that may improve their quality of life, but fear of HRT persists among these women and their doctors, despite new evidence suggesting the low probability of detrimental effects.

Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues

Gene expression profiles were studied by microarray analysis in 2 sets of archival breast cancer tissues from patients with distinct clinical outcome. Seventy‐seven differentially expressed genes were identified when comparing 30 cases with relapse and 30 cases without relapse within 72 months from surgery. These genes had a specific ontological distribution and some of them have been linked to breast cancer in previous studies: AIB1, the two keratin genes KRT5 and KRT15, RAF1, WIF1 and MSH6. Seven out of 77 differentially expressed genes were selected and analyzed by qRT‐PCR in 127 cases of breast cancer. The expression levels of 6 upregulated genes (CKMT1B, DDX21, PRKDC, PTPN1, SLPI, YWHAE) showed a significant association to both disease‐free and overall survival. Multivariate analysis using the significant factors (i.e., estrogen receptor and lymph node status) as covariates confirmed the association with survival. There was no correlation between the expression level of these genes and other clinical parameters. In contrast, SERPINA3, the only downregulated gene examined, was not associated with survival, but correlated with steroid receptor status. An indirect validation of our genes was provided by calculating their association with survival in 3 publicly available microarray datasets. CKMT1B expression was an independent prognostic marker in all 3 datasets, whereas other genes confirmed their association with disease‐free survival in at least 1 dataset. This work provides a novel set of genes that could be used as independent prognostic markers and potential drug targets for breast cancer.

Body mass index (BMI) and breast cancer: impact on tumor histopathologic features, cancer subtypes and recurrence rate in pre and postmenopausal women.

The study aims to analyze the association between body mass index (BMI) at time of diagnosis, breast cancer histopathologic features (tumor size, nuclear grade, estrogen and progesterone receptor (ER and PgR) and HER-2/neu expression, histological subtypes, Ki-67 index, lymphatic/vascular invasion, axillary nodes involvement) and incidence of different subtypes defined using hormone receptors and HER2/neu expression, according to menopausal status; to evaluate the impact of BMI on disease free survival (DFS) at multivariate analysis. A total of 2148 patients (592 premenopausal, 1556 postmenopausal) were classified into subgroups according to BMI distribution. High BMI was significantly associated with larger size tumor both in pre (p = 0.01) and postmenopausal women (p = 0.00). Obese premenopausal women showed worse histopathologic features (more metastatic axillary lymphnodes, p = 0.017 and presence of vascular invasion, p = 0.006) compared to under/normal weight group. Postmenopausal patients with BMI > 25 developed more frequently ER/PgR positive cancers (87% versus 75%, p 0.017), while no association was found in premenopausal women. We could not found any statistically significant correlation between breast cancer subtypes (luminal A, B, HER-2 and basal-like) and BMI both in pre and postmenopause. Higher BMI was significantly associated with a shorter DR-FS in postmenopausal women but the independent prognostic role of obesity was not confirmed in our analysis.

Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC)

PURPOSE OF THE STUDY A retrospective analysis on 1407 patients with invasive ductal carcinoma (IDC) and 243 invasive lobular carcinoma (ILC) was performed in order to compare the histological features, the immunohistochemical characteristics, the surgical treatment and the clinical outcome in the two groups. RESULTS ILC seems to be more likely multifocal, estrogen receptor positive, HER-2 negative and to have a lower proliferative index compared to IDC. ILC, when treated with conservative surgery, required more frequently re-excision and/or mastectomy because of positive resection margins. No difference was observed in terms of 5-year disease free survival and local relapse free survival between the two groups, in the whole series and in the subgroup of patients treated with breast-conserving treatment. CONCLUSION ILC can be safely treated with conservative surgery but a more accurate preoperative evaluation of tumor size and multifocality could be advocated, in order to reduce the re-excision rate.

Extensive Nodal Disease May Impair Axillary Reverse Mapping in Patients With Breast Cancer

PURPOSE The aim of axillary reverse mapping (ARM) is to preserve arm lymphatics in patients with breast cancer who underwent surgical axillary staging. PATIENTS AND METHODS From June 2007 to December 2008, 49 patients who required axillary dissection (AD) underwent ARM. One milliliter of patent blue dye was injected in the ipsilateral arm, and all blue nodes identified during AD were sent separately for pathologic examination. Main variables associated with the detection rates of blue lymphatics, the pathologic status of blue and nonblue nodes, and the complications of the procedure were analyzed. Results Identification rates of blue lymphatics and blue nodes were 73.5% and 55.1%, respectively. Blue node identification was influenced by the time elapsed between injection of blue dye and surgery (P = .002) but not by the learning curve of the procedure. Although the blue node was clear of metastases in 24 of 27 patients, three patients with extensive nodal metastatic involvement (ie, pN2a and pN3a) showed breast cancer metastatic cells in the blue nodes as well. The only adverse effect of the procedure was skin tattooing at the injection site, which disappeared within 4 months in almost 80% of the procedures. CONCLUSION In patients with clinically negative axillary nodes, additional study is warranted to assess whether ARM may be used to spare the lymphatics from the arm. In the presence of extensive nodal disease, this technique may identify metastatic blue nodes, which demonstrates that there is not reliable separation of arm and breast lymphatic pathways.

Clinical and radiological predictors of nipple-areola complex involvement in breast cancer patients

INTRODUCTION Nipple-areola sparing mastectomy (NSM) is increasingly used in patients with non-locally advanced breast carcinoma. Literature data on the preoperative assessment of the nipple-areola complex (NAC) are inconsistent. PATIENTS AND METHODS Out of 1359 patients submitted to total mastectomy between 2001 and 2010, we selected 61 patients whose pre-operative mammogram (MX) was available (MX group) and 39 patients who underwent preoperative breast magnetic resonance imaging (magnetic resonance imaging (MRI) group). The rate of NAC involvement, the value of MX and MRI to predict NAC involvement and the performance of the Schecters and Loewns algorithms for the prediction of NAC involvement were evaluated. RESULTS In the combined MX and MRI groups, NAC involvement was found in 14% of the cases. At univariate analysis, tumour stage (p value: 0.03), central tumour location (p value: 0.004), presence of NAC retraction (p value: 0.001) and tumour-NAC distance (p value: 0.006) were associated with NAC involvement, but only the latter parameter retained statistical significance at multivariate analysis (p value: 0.05). Tumour-NAC distance was a key predictor of NAC involvement, with a negative predictive value of 94% for MX and of 100% for MRI when the cut-off was set at 10mm. Overall, the performance of Schecters and Loewns algorithms was respectively lower and similar as compared to the original series. CONCLUSIONS Occult tumour involvement of the NAC is detected in a minority of breast cancer patients submitted to mastectomy. A tumour-NAC distance ≥ 10 mm by MRI may help select patients candidate to NSM.

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 surgeons and the patients 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.

Role of re-excision for positive and close resection margins in patients treated with breast-conserving surgery

PURPOSE To evaluate the incidence of residual disease after additional surgery for positive/close margins and the impact on the rate of local and distant recurrence. METHODS A retrospective analysis on 1339 patients treated for breast cancer with breast conserving-surgery and radiotherapy at a single Institution between 2000 and 2009 was performed. RESULTS During primary surgery 526 patients (39.3%) underwent intraoperative re-excision. At the final pathological report, the margins were positive in 132 patients (9.9%) and close in 85 (6.3%). To obtain clear margins, 142 of these women underwent a second surgery; 35 patients with positive margins (27%) and 40 with close margins (47%) did not receive additional surgery because of different reasons (patients refusal, old age, comorbidity or for focal margin involvement). At second surgery, residual disease was found in 62.9% of patients with positive margins and in 55.5% of those with close margins. At a median follow-up time of 4 years, local recurrence (LR) rate was 2.9% for patients with clear margins, 5.2% (p = 0.67) for patients with unresected close margins and 11.7% (p = 0.003) for those with unresected positive margins. The HER-2 and the basal-like subtypes had the higher rate of LR and the luminal A the lowest. CONCLUSIONS A significantly higher LR rate was found only among patients with positive margins not receiving additional surgery, but not in those with unresected close margins. Positive margins are a strong predictor for LR and need re-excision that can be avoided for close margins.

Ovarian cancer in BRCA1 and BRCA2 gene mutation carriers: analysis of prognostic factors and survival

Objectives To compare clinical–pathological characteristics and outcome between sporadic ovarian cancer and ovarian cancer in patents with hereditary breast and ovarian cancer syndrome (HBOC). Methods Twenty-four patients with ovarian cancer treated between 2000 and 2009 who tested positive for BRCA1/2 mutation (BRCA+) and a control group of 64 age-matched patients with no family history of breast/ovarian cancer (controls) were enrolled. Clinical–pathological characteristics, surgical outcome, overall (OS), and progression-free survival (PFS) were compared between the two groups. Results The high-grade serous histotype was more represented in BRCA+ than in controls (70.8% versus 53.1%) (p > 0.05). BRCA+ cancers were more frequently diagnosed at stage II than controls (20.83% versus 4.69%) (p = 0.024). Radical primary surgery was performed in 70% of women in both groups, with no difference in debulking results. In patients undergoing surgery after neoadjuvant chemotherapy, in all BRCA+ patients, optimal cytoreduction was achieved (versus 70% of the controls). PFS was significantly longer for BRCA+ patients compared to controls (60 months versus 22 months; p = 0.039). No significant difference was observed in OS between BRCA+ patients and controls. Conclusions At a median follow-up time of 46 months, BRCA+ patients have a better prognosis than controls in terms of PFS. Higher chemosensitivity of BRCA+ tumours was observed.