How to Perform Repeat Sentinel Node Biopsy Safely After a Previous Mastectomy: Technical Features and Oncologic Outcomes.

BACKGROUND: The latest National Comprehensive Cancer Network Breast Cancer Guidelines still discourage repeat sentinel node biopsy (SNB) after mastectomy, and the largest multicentric study available reports only 35 cases in the absence of previous axillary dissection (AD). METHODS: From January 2003 to November 2018, 89 patients of the European Institute of Oncology with local recurrence of breast cancer after mastectomy, free of distant metastases, with a clinically negative axilla and a negative axillary ultrasound, in absence of AD, underwent lymphatic mapping before wide local excision. RESULTS: During surgery, SNB was successful for 99% of the patients, with 14% being metastatic. Additional metastatic nodes removed by AD after a positive sentinel node occurred in 82% of cases. After a medium follow-up period of 3.7 years, the overall survival rate was 96.7%, and the disease-free survival rate was 84.4%. No axillary relapse after AD was recorded. One patient who refused human epidermal growth factor receptor 2 (HER2)-targeted treatment experienced ipsilateral axillary recurrence after a negative repeat SNB. The first axillary level was never directly irradiated because all the patients with positive repeat SNB underwent AD. For invasive luminal-like HER2-negative recurrences, the metastatic sentinel node was significantly associated with the choice to prescribe adjuvant chemotherapy (p = 0.003). CONCLUSIONS: In specialized centers, repeat axillary SNB for patients with local recurrence after mastectomy in the absence of previous AD can represent a safe option for detection and removal of occult axillary disease that would otherwise not be excised/irradiated to achieve better local control and could possibly influence the choice of adjuvant treatments.

Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a distressing side effect of cancer therapy. The trial aimed to assess feasibility and effectiveness of scalp-cooling system DigniCap® to prevent CIA in primary breast cancer patients receiving an anthracycline containing adjuvant chemotherapy (CT). METHODS: Hair loss (HL) was evaluated by patient self-assessment and by the physician according to the Dean's scale at baseline and after each cycle of CT. The primary efficacy endpoint was the patient self-assessment HL score evaluated at least 3 weeks after completing CT. A Dean's scale score of 0-2 (i.e. HL ≤50%) was considered a success. RESULTS: From July 2014 to November 2016, 139 consecutive breast cancer patients were enrolled and received at least one treatment with scalp cooling. Fifty-six out of 131 evaluated patients successfully prevented HL (43%, 95% CI: 34-51%). Twenty-four patients (32%) discontinued the scalp cooling because of alopecia or scalp-cooling related AE, three patients had missing information on CIA, and 48 patients (64%) had a HL greater than 50% after CT. No serious AEs were reported. CONCLUSIONS: DigniCap® System resulted as a promising medical device to be safely integrated in supportive care of early breast cancer patients. Longer follow-up is needed to assess long-term safety and feasibility. CLINICAL TRIAL REGISTRATION NUMBER: NCT03712696.

Immunohistochemically defined subtypes and outcome in occult breast carcinoma with axillary presentation.

The aim of this study is to evaluate the outcome of occult breast cancer (OBC) in patients with axillary presentation overall and according to the immunohistochemically defined tumour subtypes. We reviewed information on 15,490 consecutive primary breast cancer patients, who underwent surgery at the European institute of oncology between September 1997 and December 2008. Patients with OBC were compared with an equal number of patients with small invasive breast carcinomas (pT1) observed at the same institution during the same period, matched for year of surgery, age, nodal status and biological features. Eighty patients with OBC (study group) and 80 patients with early breast cancer (control group) were identified. There was no significant difference in the disease-free survival (5 years DFS 66 vs. 68% P = 0.91) and the overall survival (5 years OS 80 and 86% P = 0.99) between the OBC and control groups. A statistically significant worse outcome was observed within the group of OBC for patients with more than four involved lymph nodes and with triple negative tumours. The outcome of OBC patients is comparable with that of matched patients with small sized breast cancer. High risk of relapse and death was observed in OBC patients with triple negative tumours and extensive nodal involvement.

Pegylated Liposomal Doxorubicin (Caelyx®) as Adjuvant Treatment in Early-Stage Luminal B-like Breast Cancer: A Feasibility Phase II Trial.

BACKGROUND: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a "less intensive" or personalized approach. PATIENTS AND METHODS: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx®) as adjuvant chemotherapy. Patients who received surgery for pT1-3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m2 biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. RESULTS: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33-76), with mostly pre- and peri-menopausal (65%) and stage I-II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5-100%; interquartile range, IQR: 87.5-100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73-92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77-94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3-4.7) two distant events were observed, and all patients were alive at the date of last visit. CONCLUSIONS: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated and could be considered for further evaluation as a treatment option for patients with contraindications to standard anthracyclines or requiring a personalized, less intensive approach.

Pathological complete response after preoperative systemic therapy and outcome: relevance of clinical and biologic baseline features.

In order to evaluate the outcome of patients with breast cancer according to response after primary therapy and according to clinical and biologic baseline features, we identified patients who were treated with preoperative therapy and who underwent surgery at the European Institute of Oncology (IEO), Milan, Italy, between 1995 and 2006. The outcome of patients who achieved pathological complete remission (pCR) and patients with residual disease (RD) at final surgery was analyzed. Of the 687 patients treated with preoperative therapy, we identified 82 patients who achieved pCR (12%) and 605 patients with RD (88%). A statistically significant difference in disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) was observed for patients with pCR compared with those who had RD (5 year DFS 73% vs. 59% P = 0.029; 5 year DDFS 81% vs. 72% P = 0.085; 5 year OS 88% vs. 77% P = 0.033). At the multivariate analysis, for patients achieving pCR, large tumor size (> 5 cm) correlated with worse DFS (HR 3.18; 95% CI 1.34-7.51); clinical nodal involvement was associated with poorer DFS and DDFS (HR 6.94; 95% CI 1.62-29.73 and HR 9.87 95% CI 1.29-75.53, respectively). pCR after preoperative systemic therapy correlated with significant improved outcome. A substantial rate of relapse was observed for patients with large tumors and with clinical nodal involvement at baseline. Further improvement in adjuvant treatment might be warranted.

Investigation of 18F-FDG PET in the selection of patients with breast cancer as candidates for sentinel node biopsy after neoadjuvant therapy.

PURPOSE: The main objective of this study was to determine the role of [(18)F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) in the selection of patients with breast cancer as candidates for sentinel node biopsy (SNB) after neoadjuvant therapy. METHODS: Forty-four patients with primary breast cancer clinically classified as cT2, cT3 or cT4(a-c) cN0-N2 or cN3 M0 and with a baseline FDG PET scan positive both in the site of primary tumour and axillary lymph nodes underwent neoadjuvant therapy and then a second FDG PET scan. In the case of axillary FDG PET uptake, patients underwent axillary lymph node dissection (ALND). If the second FDG PET scan was negative for axillary involvement, SNB was performed in order to evaluate axillary lymph node status. Only in the case of SN positivity did total ALND follow. RESULTS: Specificity and positive predictive value of FDG PET for detection of axillary lymph node metastases after neoadjuvant therapy were as high as 83% (95% confidence interval: 51-97%) and 85% (95% confidence interval: 54-97%), respectively, whereas sensitivity, negative predictive value and diagnostic accuracy were inadequate for a correct staging (34, 32 and 48%, respectively). CONCLUSION: The poor sensitivity of FDG PET in detecting axillary lymph node metastases makes SNB mandatory in cases of a negative scan. The relatively high positive predictive value seems to suggest a role of FDG PET in selecting patients who, after neoadjuvant therapy, are candidates for ALND, avoiding SNB. However, this issue requires confirmation in a larger series of patients.

Invasive ductal carcinoma of the breast with the "triple-negative" phenotype: prognostic implications of EGFR immunoreactivity.

Invasive ductal carcinomas (IDC) of the breast with the triple negative phenotype (steroid hormone receptor absent, negative HER2 status) are characterized by poor clinical outcome. Additional tumor markers might allow identification of patients at higher risk. We evaluated clinical and biological features of 284 consecutive patients with pT1-3, pN1-3 M0 triple-negative IDC. Median follow-up was 70 months (interquartile range 59-94 months). Statistically significant worse disease-free and overall survival were observed in multivariate analysis, for patients with EGFR immunoreactivity in >or=50% invasive tumor cells (HR 2.39, 95% CI, 1.32-4.34, P = 0.004 for DFS; HR 2.34, 95% CI, 1.20-4.59 P = 0.01 for OS). Age >or= 70 years and PVI were additional independent predictors of reduced overall survival. EGFR immunoreactivity significantly correlates with worse prognosis in patients with triple-negative IDC, supporting further studies on the correlation between the degree of EGFR expression and outcome of triple negative breast cancer.

Increasing steroid hormone receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy.

The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0-49%, vs. ER and PgR >or=50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4 P < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5-11.6, for DFS; HR 3.6 95% CI 2.4-5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of steroid hormone receptors. Studies on tailored preoperative therapies are needed.

Infusional fluorouracil, epirubicin, and cisplatin followed by weekly paclitaxel plus bevacizumab in locally advanced breast cancer with unfavorable prognostic features.

The objective of this study was to evaluate the clinical and biological activities of bevacizumab in combination with preoperative anthracyclines and taxane-based chemotherapy in locally advanced breast cancer selected for unfavorable prognostic features. Patients with cT2-4c, cN0-2, estrogen and progesterone receptors less than 10% of the cells or cT4d and any estrogen/progesterone receptors expression received four courses of ECF-chemotherapy (epirubicin, cisplatin, fluorouracil as continuous infusion) followed by three courses of weekly paclitaxel in combination with bevacizumab. Thirty patients were included in the study. An objective response, either complete or partial, was observed in 26 patients (87%; 95% confidence interval: 69-96%), stable disease was observed in two patients (7%), and two patients (7%) progressed. A pathological complete response was obtained in 10 patients (33%; 95% confidence interval: 17-53%). Side effects related to bevacizumab with grade >or=2 included headache and hypertension. A nonstatistical significant decrease in the median value of circulating endothelial cells was observed at surgery (3.0/microl vs. 5.7/microl, P=0.19). In conclusion, high rates of both clinical and pathological responses with anthracycline-containing chemotherapy followed by weekly paclitaxel plus bevacizumab were observed in locally advanced breast cancer with unfavorable prognostic features. A non-negligible rate of progressive disease was observed, suggesting careful monitoring of the patients. Further studies evaluating the potential benefit of bevacizumab in neoadjuvant treatment need to be tested.

HER2 status in early breast cancer: relevance of cell staining patterns, gene amplification and polysomy 17.

The prevalence of HER2 amplification according to the percentage of positively stained cells, of polysomy 17 and their correlation with clinical and pathologic characteristics were retrospectively evaluated in a population of 415 breast cancers where fluorescence in situ hybridisation (FISH) was performed to clarify HER2 status previously determined by immunohistochemistry. Forty-two tumours with intense and complete staining in >50% of cells were selected from the same database as internal controls. Among the 415 cases, 233 tumours were IHC 1+, 168 tumours were 2+ and 14 tumours showed an intense and complete immunostaining in 50% of neoplastic cells. HER2 was amplified in 3/14 (21.4%) tumours with 50% and in 36/42 (85.7%) tumours with >50% of intense stained cells, (p<0.001). Polysomy 17 was detected in 77 tumours (16.85%). It was inversely correlated with the percentage of positively stained cells, but not with amplification. Patients with polysomy 17 and no amplification were significantly more likely to have tumours with favourable biological features when compared with patients with HER2 amplification. Our results suggest that FISH testing should be considered for tumours with 50% positive stained cells and that polysomy 17 without amplification is not associated with poor prognostic features.

Safety and efficacy study of metronomic vinorelbine, cyclophosphamide plus capecitabine in metastatic breast cancer: A phase II trial.

In a phase II study we assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line (naïve group) or second-line or greater therapy (pre-treated group). Eligible patients had histologically or cytologically proven, hormone-receptor positive metastatic breast cancer. The primary end point was median time to progression (TTP). A total of 43 patients in the naïve group and 65 in the pre-treated group were enrolled. The median TTP was 25.1 months in the naïve group and 11.2 months in the pre-treated group. The most frequently reported grade 2 treatment-related adverse events were leukopenia and hand and foot syndrome. Metronomic combination of cyclophosphamide, capecitabine and vinorelbine showed significant activity and good tolerability in patients hormonal receptor positive, metastatic breast cancer patients.

Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement.

BACKGROUND: Overt ipsilateral axillary lymph node metastases of breast cancer are the most significant prognostic indicators for women who have undergone surgery, yet the clinical relevance of minimal involvement (isolated tumor cells and micrometastases) of these nodes is uncertain. PATIENTS AND METHODS: We evaluated biologic features, adjuvant treatment recommendations, and prognosis for 1,959 consecutive patients with pT1-3, pN0, minimal lymph node involvement (pN1mi or pN0i+), or pN1a (single positive node) and M0, who were operated on and counseled for medical therapy from April 1997 to December 2000. RESULTS: Patients with pN1a and pN1mi/pN0i+, when compared with patients with pN0 disease, were more often prescribed anthracycline-containing chemotherapy (39.1% v 33.2% v 6.1%, respectively; P < .0001) and were less likely to receive endocrine therapy alone (9.8% v 19.4% v 41.9%, respectively; P < .0001). At the multivariate analysis, a statistically significant difference in disease-free survival (DFS) and in the risk of distant metastases was observed for patients with pN1a versus pN0 disease (hazard ratio [HR] = 2.04; 95% CI, 1.46 to 2.86; P < .0001 for DFS; HR = 2.32; 95% CI, 1.42 to 3.80; P = .0007 for distant metastases) and for patients with pN1mi/pN0i+ versus pN0 disease (HR = 1.58; 95% CI, 1.01 to 2.47; P = .047 for DFS; HR = 1.94; 95% CI, 1.04 to 3.64; P = .037 for distant metastases). CONCLUSION: Even minimal involvement of a single axillary node in breast cancer significantly correlates with worse prognosis compared with no axillary node involvement. Further studies are required before widespread modification of clinical practice.

Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with HER-2 positive metastatic breast cancer.

BACKGROUND: HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We therefore tested the activity of the combination of Trastuzumab with metronomic, low dose chemotherapy with cyclophosphamide (CTX) and methotrexate (MTX) in metastatic breast cancer (MBC). METHODS: Between April 2002 and June 2005, twenty-two patients with metastatic breast cancer with the presence of overexpression or amplification of HER2-/neu, all pre-treated with trastuzumab plus other cytotoxics, were treated with trastuzumab (6 mg/kg every three weeks) in combination with metronomic chemotherapy (MTX 2.5 mg, bid on Day 1 and Day 4 every week) and CTX (50 mg daily) (CM). RESULTS: The 22 enrolled patients are evaluable: most had an ECOG performance status of 0 (17 pts), and all were pre-treated with chemotherapy for metastatic disease; 14 had progressive disease at study entry, and 11 had progressive disease during the last trastuzumab therapy. Metastatic sites included: lung (5 pts), liver (14 pts), bone (12 pts), lymph nodes (8 pts), central nervous system (CNS) (9 pts). We observed 4 partial remission (PR) (18%, 95% CI 5-40%), 10 stable disease (SD) (46%, 95% CI 24-68%), and 8 PD (36%, CI 17-59%). The clinical benefit (RP plus RC plus SD for > or = 24 weeks) in all pts and in pts with disease resistant to previous trastuzumab therapy were 46% (95% CI, 24-68%) and 27% (95% CI, 6-61%), respectively. Median time to progression was 6 months and median duration of treatment was 5 months (range, 0,7 to 18.4 months and range, 1 to 18 months, respectively). Overall clinical toxicity was generally mild. Grade > or =2 reversible liver toxicity and leukopenia were reported in 5 and 3 pts, respectively. CONCLUSION: The combination of trastuzumab and metronomic chemotherapy is effective and minimally toxic in advanced breast cancer patients. The efficacy observed in patients with disease resistant to trastuzumab supports the need of larger trial to confirm a role of this combination to delay acquired trastuzumab resistance.

Intermittent Letrozole Administration as Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone Receptor-Positive Early Breast Cancer: A Biologic Study.

BACKGROUND: Letrozole withdrawal for 3 months might permit estrogenic stimulation in residual resistant breast cancer disease susceptible to letrozole reintroduction. We investigated the impact of a 3-month letrozole-free interval on serum estradiol levels in patients with early stage breast cancer. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor- and/or progesterone receptor-positive (> 10% of immunoreactive cells), node-negative early breast cancer were eligible. Patients received letrozole for 5 years with a 3-month treatment-free interval after the first year of therapy. The primary end point was to evaluate the increase in serum estradiol levels after a 3-month treatment-free interval. The secondary end points were the evaluations of other biologic markers (eg, follicle-stimulating hormone, luteinizing hormone, cholesterol, high-density lipoprotein, triglycerides, osteocalcin). RESULTS: From November 2007 to February 2012, 130 evaluable patients were enrolled. The median age was 61 years. Mean values of estradiol levels at time of discontinuation were 5.6 pg/mL (standard deviation 1.7). Estradiol levels increased after a 3-month treatment-free interval by a mean of 3.3 pg/mL (66%; P < .0001). Follicle-stimulating hormone and luteinizing hormone levels decreased from baseline by a mean of 7.5 mU/mL (P < .0001), and 1.4 mU/mL (P = .0062), respectively. Triglycerides decreased from baseline by a mean of 8.6 mg/dL (P = .036), and osteocalcin increased by a mean of 2.8 ng/mL (P = .013). CONCLUSION: Intermittent letrozole significantly affects estradiol levels.

Adjuvant therapy for very young women with breast cancer: response according to biologic and endocrine features.

Incidence of breast cancer in patients aged < 20 years has been estimated to be 0.1 per 100,000 women. Reported incidences are 1.4 for women aged 20-24 years, 8.1 for women aged 25-29 years, and 24.8 for women aged 30-34 years. Younger patients have been found to have a more aggressive presentation of disease at diagnosis, which is associated with dire prognoses compared with those in premenopausal older patients. Several biologic features might explain the more aggressive behavior of breast cancer in younger patients: higher grade and higher expression of Ki67, higher occurrence of vessel invasion, and less expression of estrogen and progesterone receptors. Choice of adjuvant therapies for women aged <35 years with breast cancer is based on data derived from trials on cohorts of older patients. On average, the effect of chemotherapy for premenopausal patients is substantial: recent evidence suggested that very young women with endocrine-responsive tumors had a higher risk of relapse than older premenopausal patients with similar tumors. This was not the case for patients with endocrine-nonresponsive tumors, for which effects of chemotherapy were similar across ages. Very young women with this disease are faced with personal, family, professional, and quality-of-life issues that further complicate the phase of treatment decision-making. The development of more effective therapies for very young women with breast cancer requires tailored treatment investigations and research focused on issues specific to these patients.

Residual telomerase activity: a marker of cell survival after exposure to gamma radiation in vitro.

BACKGROUND: Residual telomerase activity (TA) could be used as a marker of malignant or normal cell survival after exposure to cytotoxic agents. Therefore TA after treatment with ionizing radiation was used in a radiosensitivity assay. MATERIALS AND METHODS: Radiosensitive MOLT-4 and relatively radioresistant Jurkat leukemia cells or normal peripheral blood mononuclear cells (MNC) were irradiated with 5-160 Gy. Cell count, MTT assay and telomerase activity were evaluated on day 3 and clonogenic assay on day 10. RESULTS: In Jurkat cells, irradiation inhibited tumor growth and total TA per culture (TA/culture), but up-regulated TA per viable cell (TA/cell). TA/culture and TA/cell were profoundly depressed by irradiation of MOLT-4 or phytohemagglutinin-activated MNC. CONCLUSION: Susceptibility of normal or neoplastic cells to high-dose radiation can be monitored by evaluating residual TA/culture. In some cases, however, difficulties in the interpretation of the results could stem from radiation-induced increase of TA/cell, as observed for the Jurkat cell line.

Prevalence and clinicopathologic correlates of O6-methylguanine-DNA methyltransferase methylation status in patients with triple-negative breast cancer treated preoperatively by alkylating drugs.

BACKGROUND: Predictive factors of benefit from specific chemotherapy regimens are not currently available in triple-negative breast cancer (TNBC). MGMT (O(6)-methylguanine-DNA methyltransferase) controls DNA repair pathways, and its epigenetic silencing is used for predicting the response to the alkylating drug temozolomide in patients with glioma. MATERIALS AND METHODS: The study population was composed of 84 patients with TNBC treated with alkylating agents and evaluated for clinicopathologic parameters (tumor shrinkage and pathologic complete response [pCR]). MGMT methylation status was assessed in formalin-fixed, paraffin-embedded tumor specimens by pyrosequencing. The samples were categorized as methylated (mean methylation value > 5%), indeterminate (4%-5%), and unmethylated (≤ 3%). RESULTS: MGMT methylation status was successfully evaluated in all the cases: 58.3% were methylated; 27.4%, unmethylated; and 14.3%, indeterminate. MGMT methylation was observed in 80%, 62%, and 29% of patients showing a 100%, 99% to 30%, and < 30% tumor reduction, respectively, a trend not achieving statistical significance (P = .23). There was no association between MGMT methylation status and pCR. CONCLUSION: The present study provided evidence that pyrosequencing performs well for the evaluation of MGMT methylation even in small bioptic samples, suggesting that it could be reliably used in translational studies of preoperative clinical trials. Although there was an association trend between high methylation levels and clinical response to therapy, no statistically significant association with the pCR was found. Further studies in larger series of patients are warranted for ascertaining the putative clinical role of MGMT in patients with TNBC.

Survival outcomes in breast cancer patients with low estrogen/progesterone receptor expression.

INTRODUCTION: The prognostic value of low estrogen and progesterone receptors expression (ER/PgR 1%-10%) in early breast cancer patients is still unclear. PATIENTS AND METHODS: We retrospectively analyzed 1424 consecutive patients with HER2/neu-negative and low endocrine receptors expression early breast cancer, submitted to surgery at the European Institute of Oncology between January 1995 and December 2009. Patients were classified according to the percentage of ER/PgR expression using immunohistochemistry. Group 1 with ER/PgR < 1%, and group 2 with ER/PgR 1% to 10%. RESULTS: Group 1 (ER/PgR < 1%) included 1300 patients, and group 2 (ER/PgR 1%-10%) 124 patients. Median follow-up time was 74 months (range, 3-192 months). The 5-year disease-free survival (DFS) rate was 74% (95% confidence interval [CI], 72%-77%) for group 1, and 79% (95% CI, 70%-86%) for group 2 (P = .16). The 5-year overall survival (OS) rate was 86% (95% CI, 84%-88%) in group 1 and 90% (95% CI, 83%-95%) in group 2 (P = .13). In patients without lymph node involvement, the 5-year OS rate was 92% (95% CI, 89.5%-93.6%) for group 1 and 98% (95% CI, 90.2%-99.8%) for group 2 (P = .061). One hundred ten patients received endocrine therapy with no significant effect on DFS (P = .36) and OS (P = .30). CONCLUSION: The ER/PgR 1%-10% group had a slight, but not statistically significant, better prognosis than the ER/PgR <1% group. Further studies are needed to identify the appropriate clinical approach in this subset of patients with low ER/PgR expression (ER/PgR 1%-10%), HER2-negative early breast cancer.

Outcome of male breast cancer: a matched single-institution series.

BACKGROUND: Breast cancer occurs rarely in men, accounting for approximately 1% of all breast carcinomas. Data on prognosis principally derive from retrospective studies and from extrapolation of female breast cancer series. PATIENTS AND METHODS: A total of 99 men with invasive breast cancer were matched with 198 women with breast cancer who had surgery at the same institution from 1999 to 2010. Matching variables were year of surgery, age, primary tumor size, nodal involvement, hormone receptor status, status of HER2 (human epidermal growth factor receptor 2 [ERBB2]), Ki-67, and grade. Median follow-up was 8.6 years. RESULTS: Disease-free survival (DFS) was significantly poorer in the men (10-year DFS, 51.7% vs. 66.5%; hazard ratio [HR], 1.79; 95% CI, 1.19-2.68; P = .004). Similar results were observed for overall survival (OS) (10-year OS, 70.7% vs. 84.2%; HR, 1.79; 95% CI, 1.01-3.15; P = .043). The cumulative incidence of death for causes not related to the primary breast cancer was significantly higher for men than for women (HR, 2.87; 95% CI, 1.58-5.22; P = .001), whereas the breast cancer-specific survival (BCSS) was similar between the 2 groups (10-year BCSS, 81.5% vs. 88%; HR, 1.27; 95% CI, 0.62-2.59; P = .517). CONCLUSION: This comparative series found that men with breast cancer had a poorer DFS and OS when compared with women. The men also had a higher risk of contralateral tumors and second primaries. Appropriate counseling, surveillance, and prevention are recommended to improve survival for these individuals.

A nomogram based on the expression of Ki-67, steroid hormone receptors status and number of chemotherapy courses to predict pathological complete remission after preoperative chemotherapy for breast cancer.

BACKGROUND: Tools able to predict pathological complete response (pCR) to preoperative chemotherapy might improve treatment outcome. PATIENTS AND METHODS: Data from 783 patients with invasive ductal carcinoma treated with preoperative chemotherapy and operated at the European Institute of Oncology were used to develop a nomogram using logistic regression model based on both categorical (clinical T and N, HER2/neu, grade and primary therapy) and continuous variables (age, oestrogen receptor (ER), progesterone receptor (PgR), Ki-67 expression and number of chemotherapy courses). The performance of the resulting nomogram was internally evaluated through bootstrapping methods. Finally the model was externally validated on a patient set treated in other institutions and subsequently operated at the EIO. RESULTS: At multivariable analysis the probability of pCR was directly associated with Ki-67 expression (OR for 10% increase in the percentage of positive cells, 1.15, 95% confidence interval (CI), 1.03, 1.29) and number of chemotherapy courses (OR for one cycle increase, 1.31, 95% CI, 1.12, 1.53) and inversely associated with ER and PgR expression (ORs for 10% increase in the percentage of positive cells, 0.86, 95% CI 0.79, 0.93 and 0.82, 95% CI 0.69, 0.99, respectively). The nomogram for pCR based on these variables had good discrimination in training as well in validation set (AUC, 0.78 and 0.77). CONCLUSION: The use of a nomogram based on the number of preoperative courses, degree of Ki-67 and steroid hormone receptors expression may be useful for predicting the probability of pCR and for the design of the proper therapeutic algorithm in locally advanced breast cancer.