Prognostic factors and outcome of HER2+ breast cancer with CNS metastases.

Aim: Trastuzumab prolongs progression-free and overall survival in HER2+ breast cancer (BC), but these are associated with increased distant recurrences and central nervous system metastases (CNSm). We retrospectively evaluated outcome and prognostic factors in CNSm and non-CNSm patients. Methods: Records of HER2+ BC treated in 2000-2017 were reviewed. Results: 283/1171 (24%) HER2+ BC patients developed metastatic disease. 109/283 patients (39%) have CNSm associated with worse prognosis and increased risk of death (hazard ratio: 4.7; 95% CI: 3.5-6.4). Prognostic factors were: number of CNSm (single vs multiple lesions; 3-year overall survival 39 vs 18%; p = 0.003); brain radiation (30 vs 14%; p < 0.001); new HER2-targeting therapies (30.6 vs 22.5%; p = 0.025). Conclusion: Prognosis of BC patients with CNSm has improved using HER2-targeting therapies but remains poor.

The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries.

BRCA1 BRCA2 mutational spectrum in the Middle East, North Africa, and Southern Europe is not well characterized. The unique history and cultural practices characterizing these regions, often involving consanguinity and inbreeding, plausibly led to the accumulation of population-specific founder pathogenic sequence variants (PSVs). To determine recurring BRCA PSVs in these locales, a search in PUBMED, EMBASE, BIC, and CIMBA was carried out combined with outreach to researchers from the relevant countries for unpublished data. We identified 232 PSVs in BRCA1 and 239 in BRCA2 in 25 of 33 countries surveyed. Common PSVs that were detected in four or more countries were c.5266dup (p.Gln1756Profs), c.181T>G (p.Cys61Gly), c.68_69del (p.Glu23Valfs), c.5030_5033del (p.Thr1677Ilefs), c.4327C>T (p.Arg1443Ter), c.5251C>T (p.Arg1751Ter), c.1016dup (p.Val340Glyfs), c.3700_3704del (p.Val1234Glnfs), c.4065_4068del (p.Asn1355Lysfs), c.1504_1508del (p.Leu502Alafs), c.843_846del (p.Ser282Tyrfs), c.798_799del (p.Ser267Lysfs), and c.3607C>T (p.Arg1203Ter) in BRCA1 and c.2808_2811del (p.Ala938Profs), c.5722_5723del (p.Leu1908Argfs), c.9097dup (p.Thr3033Asnfs), c.1310_1313del (p. p.Lys437Ilefs), and c.5946del (p.Ser1982Argfs) for BRCA2. Notably, some mutations (e.g., p.Asn257Lysfs (c.771_775del)) were observed in unrelated populations. Thus, seemingly genotyping recurring BRCA PSVs in specific populations may provide first pass BRCA genotyping platform.

Predictive Factors of Eribulin Activity in Metastatic Breast Cancer Patients.

OBJECTIVES: Predictive factors of response to eribulin are lacking. We aimed to investigate the activity and safety of eribulin in a real-world population of metastatic breast cancer (MBC) patients and to identify possible predictive factors of progression-free survival (PFS) and objective response. METHODS: We retrospectively analyzed 71 eribulin-treated MBC patients. Best response rate, PFS, and adverse events (AEs) were evaluated. The impact of different clinical-pathological factors on PFS was evaluated using the Cox proportional hazards model. Predictive factors of response were identified by discriminant function analysis (DFA). RESULTS: Median PFS was 3.75 months (95% CI, 2.39-4.48); 12 patients (16.90%) achieved partial response (PR), 27 (38.03%) stable disease. The most common AEs were fatigue (25.83%), neutropenia (16.56%), and peripheral neuropathy (13.91%). A worse performance status (p = 0.025) and a higher number of metastatic organ sites (p = 0.011) were associated with a worse PFS under eribulin. Overall, in the DFA-predictive model, neutrophil-to-lymphocyte ratio at baseline, estrogen receptor, Ki67, histology, and age were predictive of PR with 100% accuracy. CONCLUSIONS: Activity and safety profiles of eribulin were consistent with literature data. Performance status and number of metastatic sites were predictive factors of PFS. DFA could be a promising tool to discriminate responses to eribulin among MBC patients.

Clinicopathological and Immunohistochemical Characteristics in Male Breast Cancer: A Retrospective Case Series.

BACKGROUND: Due to its rarity, male breast cancer (mBC) remains an inadequately characterized disease, and current evidence for treatment derives from female breast cancer (FBC). METHODS: We retrospectively analyzed the clinicopathological characteristics, treatment patterns, and outcomes of mBCs treated from 2000 to 2013. RESULTS: From a total of 97 patients with mBC, 6 (6.2%) with ductal in situ carcinoma were excluded, and 91 patients with invasive carcinoma were analyzed. Median age was 65 years (range: 25-87 years). Estrogen receptors were positive in 88 patients (96.7%), and progesterone receptors were positive in 84 patients (92.3%). HER-2 was overexpressed in 13 of 85 patients (16%). Median follow-up was 51.5 months (range: 0.5-219.3 months). Five-year progression-free survival (PFS) was 50%, whereas overall survival (OS) was 68.1%. Patients with grades 1 and 2 presented 5-year PFS of 71% versus 22.5% for patients with grade 3 disease; 5-year OS was 85.7% for patients with grades 1 and 2 versus 53.3% of patients with grade 3. Ki-67 score >20% and adjuvant chemotherapy were also statistically significant for OS on univariate analyses. Twenty-six of 87 patients (29.8%) experienced recurrent disease and 16 of 91 patients (17.6%) developed a second neoplasia. CONCLUSION: Male breast cancer shows different biological patterns compared with FBC, with higher positive hormone-receptor status and lower HER-2 overexpression. Grade 3 and Ki-67 >20% were associated with shorter OS. IMPLICATIONS FOR PRACTICE: There is little evidence that prognostic features established in female breast cancer, such as grading and Ki-67 labeling index, could be applied to male breast cancer as well. This study found that grade 3 was associated with shorter overall survival and a trend for Ki-67 >20%; this could help in choosing the best treatment option in the adjuvant setting. Many questions remain regarding the impact of HER-2 positivity on survival and treatment with adjuvant anti-HER-2 therapy. Regarding metastatic male breast cancer, the results suggest that common regimens of chemo-, endocrine and immunotherapy used in female breast cancer are safe and effective for men. Male breast cancer patients show a higher incidence of second primary tumors, especially prostate and colon cancers and should therefore be carefully monitored.

Eribulin in cutaneous breast cancer metastasis treatment: clinical activity and symptom control.

AIM: This observational study evaluated the behavior and outcome of cutaneous breast cancer metastasis treated with eribulin. PATIENTS & METHODS: From November 2012 to January 2013, oncologists completed a database with patient, tumor and treatment characteristics from 14 Italian cancer centers. Skin lesions were assessed by Response Evaluation Criteria In Solid Tumors and cutaneous symptoms by present/absent criteria. RESULTS: A total of 23 metastatic breast cancer patients with skin metastasis who were treated with eribulin were analyzed. After treatment, 43% of patients exhibited a partial response, 35% stable disease and 22% progressive disease. Regarding only the skin response, 26% obtained a complete response, 22% a partial response, 39% stable disease and 13% progressive disease. We found an improvement in symptoms, infiltration and ulceration. With a median follow-up of 6 months, median progression-free survival was 4.3 months and median overall survival was 9.1 months. CONCLUSION: The response rate of skin metastasis to eribulin treatment was coherent with systemic responses. The good clinical response in most patients reflected symptom improvement.

Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes.

Abstract. Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants. Materials and methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme. Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up. Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population.

Surgical management of BRCA-mutation carriers: A single institution experience.

INTRODUCTION: The optimal surgical management of BRCA-mutation carriers remains a subject of debate. To evaluate the appropriateness of breast cancer (BC) treatment, the oncological outcomes of BRCA-mutation carriers treated either with breast-conserving therapy (BCT) or mastectomy were compared. Additionally, the role of bilateral salpingo-oophorectomy (BSO) and potential independent predictive factors for BC treatment were analyzed. MATERIALS AND METHODS: We retrospectively reviewed all the consecutive patients with a pathogenic germline mutation in the BRCA1/2 genes tested at our Institution between July 2008 and October 2018. Primary end-points were disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: The characteristics and outcomes of 124 BRCA-associated BC patients were analyzed. Overall, 69 (55.7%) and 55 (44.3%) patients underwent BCT and mastectomy, respectively; 72 (58.1%) patients underwent BSO. After a median interval of 13.3 months, 24 patients underwent mastectomy after primary BCT. There was no significant difference in terms of DFS, DDFS, and OS between patients treated with BCT or mastectomy (p = 0.39,p = 0.27,p = 0.265, respectively). Patients treated with BSO had significantly better DDFS and OS compared to ovarian conservation (p = 0.033,p = 0.040, respectively). Three independent predictive factors for BCT were identified: age ≤41 years, genetic testing performed post-operatively, and breast tumors ≤21 mm. CONCLUSIONS: Our data suggest that BRCA-mutation carriers treated with BCT present similar oncological outcomes compared to mastectomy. Ovarian preservation decreases survival. Young BRCA-mutated patients with small BCs may not need up-front mastectomy, and BSO might be performed when ovarian cancer risk epidemiologically rises and potential reproductive desire is fulfilled.

Post-Biopsy Cell-Free DNA From Blood: An Open Window on Primary Prostate Cancer Genetics and Biology.

Circulating cell-free DNA (ccfDNA), released from normal and cancerous cells, is a promising biomarker for cancer detection as in neoplastic patients it is enriched in tumor-derived DNA (ctDNA). ctDNA contains cancer-specific mutations and epigenetic modifications, which can have diagnostic/prognostic value. However, in primary tumors, and in particular in localized prostate cancer (PCa), the fraction of ctDNA is very low and conventional strategies to study ccfDNA are unsuccessful. Here we demonstrate that prostate biopsy, by causing multiple injuries to the organ, leads to a significant increase in plasma concentration of ccfDNA (P<0.0024) in primary PCa patients. By calculating the minor allele fraction at patient-specific somatic mutations pre- and post-biopsy, we show that ctDNA is significantly enriched (from 3.9 to 164 fold) after biopsy, representing a transient "molecular window" to access and analyze ctDNA. Moreover, we show that newly released ccfDNA contains a larger fraction of di-, tri- and multi-nucleosome associated DNA fragments. This feature could be exploited to further enrich prostate-derived ccfDNA and to analyze epigenetic markers. Our data represent a proof-of-concept that liquid tumor profiling from peripheral blood performed just after the biopsy procedure can open a "valuable molecular metastatic window" giving access to the tumor genetic asset, thus providing an opportunity for early cancer detection and individual genomic profiling in the view of PCa precision medicine.

Clinical predictors of cardiac toxicity in HER2-positive early breast cancer patients treated with adjuvant s.c. versus i.v. trastuzumab.

BACKGROUND: Few data are available about real-life cardiotoxicity associated with s.c. versus i.v. trastuzumab treatment of early-stage, HER2-positive breast cancer, and little is known about its predisposing factors. PATIENTS AND METHODS: We retrospectively reviewed data of 363 adult patients treated with adjuvant trastuzumab for HER2-positive breast cancer. Univariate statistical analysis was performed, and a multivariable logistic model was developed to identify independent risk factors of cardiac toxicity. RESULTS: Within 5 years, the overall incidence of events meeting our criteria was 11.8%, and an early discontinuation of trastuzumab was recorded in 20 patients (5.5%). No cases of congestive heart failure occurred, neither multiple events per patient were observed. A total of 184 patients received i.v. and 179 received s.c. trastuzumab. Compared with the s.c. formulation, a higher cardiotoxicity rate for the i.v. administration (15.2% vs 8.4%) was found, and particularly in those patients with cardiovascular risk factors (19.3% vs 8.7%), at the univariate and multivariate analyses. Although more patients with prior anthracycline-based chemotherapy experienced cardiac events, the association of this therapy with cardiac events was not significant. The incidence of cardiac events was not influenced by anthropometric data (e.g. body mass index) or a diagnosis of diabetes mellitus. 5-year event-free survival was 91.7% in the overall population; event-free survival rates were similar between the s.c. and the i.v. groups. CONCLUSION: Our study shows a more favorable safety profile of s.c. versus i.v trastuzumab administration. The use of s.c. trastuzumab could be advisable in at-risk patients.

Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy.

Germline pathogenic variants (PVs) in the BRCA1 or BRCA2 genes cause high breast cancer risk. Recurrent or founder PVs have been described worldwide including some in the Bergamo province in Northern Italy. The aim of this study was to compare the BRCA1/2 PV spectra of the Bergamo and of the general Italian populations. We retrospectively identified at five Italian centers 1019 BRCA1/2 PVs carrier individuals affected with breast cancer and representative of the heterogeneous national population. Each individual was assigned to the Bergamo or non-Bergamo cohort based on self-reported birthplace. Our data indicate that the Bergamo BRCA1/2 PV spectrum shows less heterogeneity with fewer different variants and an average higher frequency compared to that of the rest of Italy. Consistently, four PVs explained about 60% of all carriers. The majority of the Bergamo PVs originated locally with only two PVs clearly imported. The Bergamo BRCA1/2 PV spectrum appears to be private. Hence, the Bergamo population would be ideal to study the disease risk associated with local PVs in breast cancer and other disease-causing genes. Finally, our data suggest that the Bergamo population is a genetic isolate and further analyses are warranted to prove this notion.

Four new cases of double heterozygosity for BRCA1 and BRCA2 gene mutations: clinical, pathological, and family characteristics.

Double heterozygosity (DH) for BRCA1 and BRCA2 mutations is a very rare finding, particularly in non-Ashkenazi individuals, and only a few cases have been reported to date. In addition, little is known on the pathological features of the tumors that occur in DH cases and on their family history of cancer. Four carriers of pathogenic mutations in both BRCA1 and BRCA2 were identified among women who underwent genetic counseling for hereditary susceptibility to breast and ovarian carcinoma at three different Italian institutions. Clinical, pathological, and family history data were collected from medical records and during genetic counseling sessions. All identified DH cases developed breast carcinoma and three of them were also diagnosed with ovarian carcinoma. Mean ages of breast and ovarian cancer diagnosis were 42.7 and 48.6 years, respectively. The majority of breast cancers showed a BRCA1-related phenotype, being negative for hormone receptors and HER2. Two cases reported different gastrointestinal tumors among relatives. Although the individuals described in this study show more severe clinical features in comparison to previously reported BRCA1 and BRCA2 DH cases, our observations support the hypothesis of a non specific phenotype of DH cases in terms of age of disease onset. In addition, our observations indicate that in DH patients breast carcinogenesis appears to be driven mainly by the mutations in BRCA1. The possible association of DH for BRCA gene mutations with gastrointestinal tumors is in keeping with previous reports, but needs to be confirmed by further analyses.

Biological Characteristics and Long-term Outcomes in Node-negative Breast Cancer.

BACKGROUND: Because the risk of relapse of node-negative breast cancer (BC) is varying, we evaluated the prognosis of patients with this disease and the factors associated with increased risk of relapse. PATIENTS AND METHODS: The clinical charts of patients with BC with evidence of negative nodes and with a potential ≥ 5-year follow-up were retrospectively reviewed. RESULTS: We analyzed 1276 patients. Over a median follow-up of 71.6 months (range, 1-227.2 months), we observed 159 events of relapse or death. The median RFS was 170 months. The median overall survival (OS) was 192 months. At univariate analysis, older age, negative hormonal receptors, larger tumor size and higher proliferation index (Ki67) were associated with worse recurrence-free survival (RFS) and OS (P < .05); higher grading was associated with worse RFS (P = .01). At multivariate analysis for RFS, age, Ki67 and tumor size confirmed their independent prognostic role. At multivariate analysis for OS, age and positive hormonal receptors showed an independent prognostic role. We observed no differences in prognosis between human epidermal growth factor receptor 2 (HER2) positive and triple-negative (TN) BC, but TNBC showed a worse OS compared with luminal-like BC. CONCLUSIONS: In node-negative BC, age, hormone receptor status, tumor size and Ki67 were prognostic factors. The TNBC subtype was not associated with poorer prognosis compared with the HER2-positive subtype, but showed a worse OS compared with luminal-like BC.

High incidence of hypocalcemia and serum creatinine increase in patients with bone metastases treated with zoledronic acid.

BACKGROUND: Zoledronic acid belongs to the new generation of bisphosphonates with demonstrated clinical benefit for the treatment of bone metastases from different kinds of neoplasms. Hypocalcemia and serum creatinine elevation are expected adverse events during this therapy. The monitoring of serum calcium and creatinine is therefore recommended. The primary aim of this study was to establish the actual incidence of hypocalcemia and serum creatinine elevation during treatment with zoledronic acid. Skeletal-related events and side effects were also assessed. METHODS: Serum creatinine and calcium levels were evaluated in 240 consecutive patients (83 males, 157 females; mean age, 62 years) with metastatic bone lesions from different solid tumors treated with zoledronic acid. RESULTS: Overall, 93 of 240 patients (38.8%) developed hypocalcemia, which was grade (G)1 in 45 patients (48.4%), G2 in 37 patients (39.8%), G3 in 10 patients (10.8%), and G4 in one patient (1.1%). The median time to occurrence of hypocalcemia (any grade) was 2.3 months after the beginning of the treatment (range, 0-34.9 months). Increased serum creatinine was observed in 33 of 240 patients (13.7%), of whom 19 had G1 (57.6%), 11 had G2 (33.3%), and three had G3 (9.1%). The median time to serum creatinine increase (for any grade) was 4.7 months (range, 0-29.2 months). CONCLUSIONS: Our analysis shows a high incidence of hypocalcemia and increased serum creatinine level during treatment with zoledronic acid. These results strongly support the need for accurate monitoring of plasma calcium and creatinine levels.

Platinum salts in the treatment of BRCA-associated breast cancer: A true targeted chemotherapy?

Germline pathogenic mutations in breast cancer (BC) susceptibility genes (gBRCA1/2) are the most frequent inherited alterations in BC and are involved in the homologous recombination pathway, the principal mechanism of DNA double strand break repair. Platinum salts which act as DNA cross-linking agents are therefore more likely to be active in BRCA-deficient tumors. Women with gBRCA-associated tumors, particularly with triple negative BC, receiving neoadjuvant platinum containing regimens achieved higher pCR rates as compared to wild-type BC. However in two large randomized trials the addition of carboplatin significantly increased pCR rate only in wild-type tumors. On the contrary, the randomized TNT trial showed a significant benefit for carboplatin vs docetaxel in terms of response rate and PFS specifically in patients with advanced gBRCA -associated tumors. Biomarkers of sensitivity to DNA damaging agents beyond gBRCA mutations predicting activity of platinum salts have been proposed and should be validated prospectively.

Never too old to fight breast cancer: A case report.

RATIONALE: Breast cancer is the most common cancer affecting females worldwide and its lifetime risk increases with age. Human epidermal growth factor receptor gene-2 (HER-2) positive breast cancer represents about 20% of all breast cancers, 1 out of 10 is diagnosed in women over 70 years of age. It tends to be more aggressive and to spread more quickly than other subtypes, but the introduction in clinical practice of new anti-HER-2 agents combined with chemotherapy has significantly improved progression free and overall survival. Elderly patients are frequently undertreated because of concerns about their age, performance status, and comorbidities. Here, we report a case of an octogenarian patient treated with T-DM1 with brilliant results. PATIENT CONCERNS: An 87 years old woman affected with HER-2 positive breast cancer presented progression of disease with lymph node and skin metastases after 3 lines of chemoimmunotherapy. DIAGNOSES: Breast cancer in elderly patient, lymph node, and skin metastases. INTERVENTIONS: Chemoimmunotherapy (trastuzumab emtansine). OUTCOME: Objective response of the disease and significant clinical benefit. LESSONS: This case clearly suggests that age and comorbidities do not always represent an absolute contraindication to combined treatments.

Utility of 18F-FDG PET and contrast-enhanced CT scan in the assessment of residual liver metastasis from colorectal cancer following adjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy has been successfully used in the treatment of patients with colorectal liver metastases. The selection of patients for surgical resection after chemotherapy still poses a significant clinical challenge. (18)F-FDG PET is a useful tool in the assessment of liver metastases but the data regarding its sensitivity after chemotherapy is scarce. Our aim was to assess the value of this imaging modality in the selection of patients with colorectal liver metastasis for surgery following adjuvant chemotherapy. MATERIAL AND METHODS: We reviewed the diagnostic performances of (18)F-FDG PET and contrast-enhanced CT scan data from patients with colorectal liver metastases following treatment with chemotherapy. Nineteen patients (12 males, 7 females; median age 61 years; range 41-79) were evaluated. Chemotherapy regimens were: FOLFOX (14 patients), FOLFIRI (3 patients), 5-FU/FA (1 patient) and UFT-irinotecan-oxaliplatin (1 patient). Median time between end of chemotherapy and CT scan was 3.4 weeks, between end of chemotherapy and PET was 5.9 weeks and between end of chemotherapy and surgery was 9.9 weeks. All patients underwent surgery and had histopathological confirmation of liver lesions. Nine patients had segmentectomy, 2 patients had wedge resection, 5 patients had right hepatectomy and 3 patients had explorative laparotomy with liver biopsies. RESULTS: Data from all 19 patients, comprising 65 liver lesions, were confirmed by histo-pathology. Results on a per-lesion basis showed a sensitivity of 62% for (18)F-FDG PET and 70% for CT scan. A complete agreement between (18)F-FDG PET or CT scan and histology was documented in 5 and 3 patients, respectively. The sensitivity of (18)F-FDG PET was shown to increase for lesions larger than 1 cm (74% vs. 18%). CONCLUSIONS: These results suggest that (18)F-FDG PET and CT scan have sub-optimal sensitivity in the evaluation of colorectal liver lesions after neo-adjuvant chemotherapy, especially for lesions < 1 cm. The combined use of the two imaging techniques does not significantly increase the sensitivity of lesion detection.

Controversies in clinicopathological characteristics and treatment strategies of male breast cancer: A review of the literature.

Male breast cancer (MaBC) is a rare disease, accounting for less than 1% of malignancies in men. For this reason, literature data on its clinicopathological characteristics are very heterogeneous and treatment strategies have mostly been extrapolated from the female counterpart. However, immunohistochemical peculiarities of MaBC have recently emerged, defining it as a distinct entity from female breast cancer (FBC), thus requiring a tailored clinical approach. MaBC appears to be more often hormone receptor positive than FBC, while data on HER2 status still remain inconclusive, indicating a possible higher incidence of HER2 alterations. Treatment strategies for MaBC have evolved and less invasive local treatments such as lumpectomy and sentinel lymph node biopsy have become part of everyday clinical practice, while there are still controversies on the indication of radiotherapy, especially after mastectomy. Similarly, differences between male and female hormonal status have raised some concerns in the use of aromatase inhibitors in male patients and the choice of best endocrine therapy is still controversial.

Chemotherapy with mitomycin C and capecitabine in patients with advanced colorectal cancer pretreated with irinotecan and oxaliplatin.

AIMS AND BACKGROUND: To assess the activity and tolerability of the combination of mitomycin C and capecitabine in patients with metastatic colorectal cancer after failure of irinotecan and oxaliplatin-containing regimens. METHODS: We retrospectively reviewed 28 patients with pretreated advanced colorectal cancer who had been treated with mitomycin C, 6 mg/m2 on day 1, and capecitabine, 1900 mg/m2 on days 1-14, every 3 weeks. Tumor assessment was performed every 3 cycles, toxicity assessed at each cycle. RESULTS: Main patient characteristics were median age, 61 years (range, 35-73); male/female ratio, 16/12; single metastatic site involvement, 5/28 (18%); > or =3 metastatic sites, 10/28 (36%). Ninety-six courses of therapy were given (median number, 3; range, 1-9). Twenty-six patients were assessable for response, and all were assessable for toxicity. There was 1 partial response (4%) and 12 had stable disease (43%). Median time to progression was 2 months (range, 1-9) and median overall survival was 6 months (range, 1-29+), with a 1-year overall survival rate of 25%. The regimen was very well tolerated without significant hematological toxicity. CONCLUSIONS: Our results are disappointing. Despite the good safety profile, they do not support further investigation or the routine use of this regimen in this setting.

Aromatase inhibitors in premenopause: Great expectations fulfilled?

Tamoxifen and GnRH analogues (GnRHa) represent the mainstay of endocrine manipulations in premenopausal women. The estrogen blockade obtained by aromatase inhibitors (AIs) plus GnRHa suppresses circulating estrogens more deeply than tamoxifen plus GnRHa. Retrospective and prospective evidence confirm a substantial activity for AIs and GnRHa in locally advanced and metastatic breast cancer. In early breast cancer inconsistent evidence emerged from 2 large randomized studies with anastrozole performing as tamoxifen in terms of DFS, but significantly worse as of OS while exemestane outperformed tamoxifen as of DFS particularly in very young and high-risk women. These findings support the use of AIs plus GnRHa in advanced breast cancer while long term efficacy and safety data are expected to define the appropriate indication of AIs in early breast cancer. In addition the clinical significance of persistent circulating estrogens and long term effects of estrogen deprivation in young women need further clarification.