Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Feasibility and oncological safety of sentinel node biopsy in breast cancer patients with a local recurrence.

OBJECTIVES: To investigate the role and feasibility of sentinel lymph node biopsy (SLNB) in breast cancer patients with a local recurrence and no clinically positive axillary lymph nodes. MATERIALS AND METHODS: A total of 71 patients underwent SLNB for breast cancer recurrence. At first surgery, they had received SLNB (46.5%), axillary lymph node dissection (ALND) (36.6%) or no axillary surgery (16.9%). RESULTS: Lymphatic migration was successful in 53 out of 71 patients (74.6%) and was significantly higher in patients with previous SLNB or no axillary surgery than in those with previous ALND (87.9% vs. 53.8%; p = 0.009). Aberrant lymphatic migration pathways were observed in 7 patients (13.2%). The surgical SLNB was successfully performed in 51 patients (71.8%). In 46 patients (90.2%) the SLN was histologically negative, in 3 patients (5.9%) micrometastastatic and in 2 patients (3.9%) macrometastatic. The 2 patients with a macrometastates in SLN underwent ALND, In 4 out of the 18 patients with failure of tracer migration ALND, performed as surgeon's choice, did not find any metastatic node. After a median follow-up period of 39 months (range: 2-182 months), no axillary recurrence has been diagnosed. CONCLUSION: A SLNB in patients with locally recurrent breast cancer, no previous ALND and negative axillary lymph nodes is technically feasible and impacts on the ALND rate. In patients who at primary surgery received ALND, migration rate is significantly lower, aberrant migration is frequent and no clinically useful information has been obtained.

Secondary cytoreductive surgery, hyperthermic intraperitoneal intraoperative chemotherapy, and chemotherapy alone: a retrospective comparison of alternative approaches in relapsed platinum sensitive ovarian cancer.

INTRODUCTION: The best treatment for relapsed platinum sensitive epithelial ovarian cancer (EOC) is controversial. The aim of the study was to compare progression-free survival (PFS) and overall survival (OS) in platinum-sensitive EOC patients treated with chemotherapy alone (CTA), secondary cytoreductive surgery (SCR) or SCR plus hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC). MATERIALS AND METHODS: Retrospective analysis of the clinical outcome of 46 EOC patients with at least 30 months of follow-up. RESULTS: Median follow-up time was 32 months for the CTA group, 30 months for the SCR group, and 45 months for the SCR + HIPEC group. Fifteen recurrences were observed in the CTA group, seven in the SCR group, and 16 in the SCR + HIPEC group. The median time elapsed between first and second recurrence (PFI-2) was significantly higher among patients treated with SCR + HIPEC, in comparison with patients treated with CTA (p = 0.012 andp = 0.017, respectively). On the contrary, PFI-2 did not significantly differ between the SCR and SCR + HIPEC groups (p = 0.877). A statistically significant difference in OS favouring SCR + HIPEC in comparison with CTA (p = 0.04) was observed. CONCLUSIONS: SCR HIPEC compared with CTA improves PFI-2 in patients with platinum-sensitive EOC recurrence. SCR + HIPEC might also improve OS in comparison with CTA. No improvement in favor of SCR + HIPEC vs SCR was observed,. These results further support the need of a randomized trial comparing chemotherapy with SCR ± HIPEC in this setting.

TOP2A gene copy gain predicts response of epithelial ovarian cancers to pegylated liposomal doxorubicin: TOP2A as marker of response to PLD in ovarian cancer.

OBJECTIVE: The treatment of platinum resistant/refractory epithelial ovarian cancer (EOC) is a challenge for oncologists. One of the most utilized drugs in these patients is pegylated liposomal doxorubicin (PLD). As PLD is active only in a small subset of patients and causes side effects, selection of responsive patients is an unmet need and might be guided by the status of the DNA topoisomerase II alpha (TOP2A) that is poisoned by the drug. METHODS: From 176 ovarian cancers treated in three institutions, we selected 38 patients treated with PLD monotherapy as second/third line of treatment. TOP2A gene copies were measured using Fluorescent In Situ Hybridization (FISH) and expression evaluated using immunohistochemistry. Patients' derived xenografts (PDXs) of ovarian cancers were used to assess the correlation between TOP2A protein expression and response to PLD. RESULTS: Clinical data showed that TOP2A gene gain that is paralleled by increased expression of the protein, was associated with a higher probability of clinical benefit from PLD. Treatment of PDXs demonstrated that only xenografts showing a high percentage of TOP2A expressing cells underwent tumor shrinkage when treated with PLD. CONCLUSIONS: These data show that TOP2A gene gain and protein over-expression might predict activity of PLD in platinum resistant/refractory EOC.

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.

Body mass index and circulating oestrone sulphate in women treated with adjuvant letrozole.

BACKGROUND: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. METHODS: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. RESULTS: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m(-2); 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m(-2); 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m(-2); and 43.3 (23.0-81.7, n=16) when ≥35.0 kg m(-2). No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. CONCLUSIONS: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patients.

Accelerated partial breast irradiation using 3D conformal radiotherapy: toxicity and cosmetic outcome.

PURPOSE: The aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: 84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The dose-volume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale. RESULTS: Median patient age was 66 years (range 51-87). Median follow-up was 36.5 months (range 13-83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p = 0.33) or irradiated volume (p = 0.45). CONCLUSIONS: APBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse.

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.

Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus in postmenopausal women with early breast cancer treated with letrozole.

Estrogen synthesis suppression induced by aromatase inhibitors in breast cancer (BC) patients may be affected by single nucleotide polymorphisms (SNPs) of the gene encoding aromatase enzyme, CYP19A1. We assessed the association between plasma estrone sulfate (ES), letrozole treatment, and four SNPs of CYP19A1 gene (rs10046 C>T, rs4646 G>T, rs749292 C>T, rs727479 T>G) which seem to be related to circulating estrogen levels. Patients were enrolled into a prospective, Italian multi-center clinical trial (Gruppo Italiano Mammella, GIM-5) testing the association of CYP19A1 SNPs with the efficacy of letrozole adjuvant therapy, in postmenopausal early BC patients. SNPs were identified from peripheral blood cell DNA. Plasma ES concentrations were evaluated by Radio Immuno Assay. Blood samples were obtained immediately before letrozole therapy (N = 204), at 6-weeks (N = 178), 6 (N = 152) and 12-months (N = 136) during treatment. Medians (IQR) of ES were 160 pg/mL (85-274) at baseline, 35 pg/mL (12-64) at 6-weeks, 29 pg/mL (17-48) at 6 months and 25 pg/mL (8-46) after 12 months treatment. No statistically significant association was evident between polymorphisms and ES circulating levels during letrozole therapy. Letrozole suppression of the aromatase enzyme function is not affected by polymorphisms of CYP19A1 gene in postmenopausal BC patients.

Role of MRI (magnetic resonance imaging) versus conventional imaging for breast cancer presurgical staging in young women or with dense breast.

AIMS: The role of magnetic resonance imaging (MRI) in the local staging of breast cancer is currently uncertain. The purpose of this prospective study is to evaluate the accuracy of preoperative MRI compared to conventional imaging in detecting breast cancer and the effect of preoperative MRI on the surgical treatment in a subgroup of women with dense breasts, young age, invasive lobular cancer (ILC) or multiple lesions. METHODS: Between January 2006 and October 2007, 91 patients with newly diagnosed breast cancer underwent preoperative clinical breast examination, mammography, bilateral breast ultrasonography and high-resolution breast MRI. All patients had histologically verified breast cancer. The imaging techniques were compared using the final pathological report as gold standard. RESULTS: The sensitivity of MRI for the main lesion was 98.9%, while for multiple lesions sensitivity was 90.7% and specificity 85.4%. After preoperative MRI, 13 patients (14.3%) underwent additional fine needle/core biopsies, 9 of whom had specimen positive for cancer. Preoperative MRI changed the surgical plan in 26 patients: in 19.8% of the cases breast conservative surgery was converted to mastectomy and in 7.7% of the patients a wider excision was performed. At a mean follow-up of 48 months, 2 local recurrences occurred (local failure rate = 2.5%). CONCLUSIONS: Enhanced sensitivity of breast MRI may change the surgical approach, by increasing mastectomy rate or suggesting the need of wider local excision. MRI can play an important role in preoperative planning if used in selected patients with high risk of multifocal/multicentric lesions. However, the histologic confirmation of all suspicious findings detected by MRI is mandatory prior to definite surgery.

Non-hormonal treatment of hot flushes in breast cancer survivors: gabapentin vs. vitamin E.

OBJECTIVES: To assess the efficacy and the tolerability of gabapentin 900 mg/day compared to vitamin E for the control of vasomotor symptoms in 115 women with breast cancer. The secondary objective was to evaluate the effect of the treatments on the quality of sleep and other aspects of the quality of life. METHODS: A hot flush diary was completed daily; sleep quality and other menopausal symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI), the Menopause Rating Scale (MRS) and the SF-36 Health Survey. RESULTS: The prescribed treatment with gabapentin was never started by 28.3% of the patients and was interrupted by 28% for side-effects (dizziness and somnolence). Among the women allocated to vitamin E, 16.36% never started therapy and 34.78% dropped out because of inefficacy. Hot flush frequency and score decreased by 57.05% and 66.87%, respectively (p < 0.05) in the gabapentin group. The effect of vitamin E was fairly small: hot flush frequency and score were reduced by 10.02% and 7.28%, respectively (p > 0.05). Gabapentin was also particularly effective in improving the quality of sleep (PSQI score reduction: 21.33%, p < 0.05). CONCLUSION: Gabapentin appears to be effective for the treatment of hot flushes with a favorable effect on quality of sleep. Vitamin E has only marginal effect on vasomotor symptoms.

Indications for breast magnetic resonance imaging. Consensus document "Attualità in senologia", Florence 2007.

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.

Clinical outcome of adjuvant endocrine treatment according to PR and HER-2 status in early breast cancer.

Patients with estrogen receptor (ER)+/progesterone receptor (PR)- and/or HER-2 overexpressing breast carcinomas may derive lower benefit from endocrine treatment. We examined retrospectively data from 972 breast cancer patients who received tamoxifen (725), tamoxifen + Gn-RH analogs (127) and aromatase inhibitors (120) as adjuvant treatments. ER+/PR- versus ER+/PR+ tumours were characterised by larger size (P = 0.001), higher tumour grade (P = 0.001), higher Ki-67 expression (P = 0.001) and lower mean ER (P = 0.000) and HER-2 expression (P = 0.000). At univariate analysis, tumour grading [hazard ratio (HR) = 4.0; 95% confidence interval (CI) = 1.4-11.1; P = 0.007], nodal status (HR = 3.4; 95% CI 1.2-5.7; P = 0.000), tumour diameter (HR = 2.9; 95% CI 1.7-4.7; P = 0.000) lack of PR expression (HR = 2.1; 95% CI 1.3-3.4; P = 0.002) and HER-2 overexpression (HR = 1.9; 95% CI 1.0-3.5; P = 0.03), as well as Ki 67 expression (HR = 1.7; 95% CI 1.0-2.7; P = 0.04) were associated with shorter disease-free survival (DFS). At the multivariate analysis, nodal status (HR = 3.6; 95% CI 1.9-6.8; P = 0.0001), lack of PR expression (HR = 2.3; 95% CI 1.3-4.0; P = 0.003) and tumour diameter (HR = 2.1; 95% CI 1.1-3.8; P = 0.018) retained their prognostic significance, whereas HER-2 overexpression was associated with a trend towards shorter DFS that was of borderline statistical significance (HR = 2.0; 95 % CI 1.0-3.9; P = 0.05). Our data suggest that lack of PR expression and HER-2 overexpression are both associated with aggressive tumour features, but the prognostic information of PR status on the risk of recurrence in endocrine-treated breast cancer patients is stronger.

Concurrent radiotherapy does not affect adjuvant CMF delivery but is associated with increased toxicity in women with early breast cancer.

We evaluated whether concurrent radiotherapy (RT) affected delivery and toxicity of adjuvant intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in women with operable breast cancer. The medical charts of 321 consecutive breast cancer patients who received CMF either alone for 6 cycles, or for 4 cycles following of an anthracycline (A-CMF) were reviewed. One hundred forty-four women underwent radiotherapy concurrently with CMF. Optimal CMF delivery (success as opposite to failure) was defined as the combined achievement of an average relative dose intensity (aRDI) > or = 85% and an average percent of the total dose (aPTD) > or = 90% for the three drugs in the CMF regimen. Multivariate logistic regression analysis showed that concurrent-RT did not affect CMF delivery (OR for success 1.391 p=0.230). The sequential A-CMF regimen (OR for success 0.208, 95% C.I. 0.120-0.360, p<0.001) and age > or = 56 (OR for success 0.351, 95% C.I. 0.200-0.161, p<0.001) were independently associated with suboptimal CMF delivery. Moreover, concurrent RT was independently associated with increased leukopenia, thrombocytopenia, upper abdominal pain, mucositis and fatigue. Our retrospective analysis suggests that concurrent-RT has no impact on optimal CMF delivery, but it increases the burden of CMF-related toxicity.

Evaluation of low-dose venlafaxine hydrochloride for the therapy of hot flushes in breast cancer survivors.

OBJECTIVE: To evaluate the efficacy and tolerability of long-term treatment with venlafaxine at low dose for the reduction of vasomotor symptoms in breast cancer survivors. DESIGN: Forty consecutive breast cancer patients suffering troublesome hot flushes have been treated for 8 weeks with venlafaxine XR 37.5 mg/day in an open-label study. Vasomotor symptoms have been evaluated before starting treatment and every 4 weeks with a hot flushes diary pointing out the number and the severity of vasomotor symptoms. A Beck Depression Inventory (BDI) was completed at baseline and at the end of the treatment. RESULTS: Thirty patients had completed the first 4 weeks of treatment, reporting a reduction of hot flushes frequency of 39% as compared to baseline (p<0.001). After 8 weeks of treatment, a further significant reduction was observed both for the hot flushes frequency (-53%; p<0.001) and for the hot flushes score (-59%; p<0.001), a measure which reflects both the number and the severity of hot flushes. Very few side effects were reported, mostly nausea in the first 2 weeks of assumption and mouth dryness. Only 23 women had completed BDI at week 8; a reduction of 23% was observed (p=0.000). CONCLUSION: Venlafaxine is an effective treatment for the relief of vasomotor symptoms in patients previously treated for breast cancer. A favourable effect is maintained also in those patients using tamoxifen as adjuvant therapy. The use of the low dose (37.5 mg/day) is associated with minimal side effects and produces a good improvement in hot flushes if pursued over 8 weeks.

The influence of hormone replacement therapy on the pathology of breast cancer.

AIM OF THE STUDY: To assess whether the pathological characteristics of breast carcinomas arising in post-menopausal women who ever used hormonal replacement therapy (HRT) differ from those of post-menopausal patients who never used HRT. MATERIALS AND METHODS: Six hundred and forty three consecutive breast cancer patients were entered in a case control-study. Cases were represented by 111 breast cancer patients who had used or were using HRT at the time of diagnosis, while the remaining 532 patients who never used HRT were chosen as controls. RESULTS: Tumour diameter was smaller in HRT users (17.6 vs 22.1 mm; p=0.002) and tumours of lobular histology were almost twice more frequent among HRT users as in 'never users' (21 vs 12%; p=0.01). No differences were found in grading, hormonal receptor status and axillary nodal status. The expression of c-erb B-2, p53, Ki67 and PS2 measured by immunohistochemistry was similar in the two groups. CONCLUSIONS: Our findings suggest that HRT use may modify the pathological presentation of breast cancer. Further studies are indicated, while other clinical-pathological characteristics did not differ according to HRT use.

Management of risk of breast carcinoma in postmenopausal women.

Breast carcinoma is the most frequent tumor in the female population. Many factors can influence the risk of breast cancer; some of them, such as old age and breast cancer 1/2 (BRCA1/BRCA2) gene mutations, are associated with a fourfold increase in risk. A previous diagnosis of atypical ductal or lobular hyperplasia or having a first-degree relative with a carcinoma are factors associated with a two- to fourfold increase in risk. A relative risk between 1 and 2 is associated with longer exposure to endogenous hormones as a result of early menarche, late menopause and obesity, or with recent and prolonged use of hormone replacement therapy (HRT) or with behavioural factors such as high alcohol and fat intake. Is it possible to modify breast cancer risk in postmenopausal women? Risk factors related to lifestyle can be changed, even if it is not clear whether modifying these behavioural factors during the postmenopausal period will influence the overall breast cancer risk. For instance, the influence of exogenous hormones throughout life (both oral contraceptives and HRT) should be evaluated according to the individual risk-benefit ratio. The problem is even more complex for women who carry genetic mutations and for those who have close relatives with breast cancer, who may be candidates for risk reduction strategies. Prophylactic bilateral mastectomy is still controversial, but is frequently offered to or requested by this group of women and may be indicated in BRCA1/BRCA2 carriers. Chemoprevention with tamoxifen and with the new selective estrogen receptor modulators, namely raloxifene, is very promising and deserves a thorough discussion for all high-risk women.

Sentinel node dissection as definitive treatment for node negative breast cancer patients.

AIMS: Negative sentinel node may predict tumour-free axillary nodes in breast cancer. We report the performance of sentinel node dissection at our Institution. METHODS: We analysed data from 212 consecutive women with primary invasive breast tumours less than 3 cm in diameter and no axillary lymphadenopathy who underwent radioguided sentinel node dissection by means of 99mTc-colloidal albumin between 1999 and 2002. Completion axillary node dissection was performed if sentinel nodes contained metastases or if no sentinel nodes were identified. RESULTS: Sentinel nodes were identified in 207/212 of the patients. Fifty-seven patients had tumour-positive sentinel nodes. Only tumour diameter showed significant association with sentinel node status (p<0.000). Per-operative histologic evaluation had a sensitivity of 67.3% and a negative predictive value of 90.4%. No subset of sentinel node positive patients was identified for whom axillary node dissection could be safely avoided. No recurrences were detected at a median follow-up of 15 months. CONCLUSION: Radioguided sentinel node dissection offers a reliable way to assess nodal status in most breast cancer patients. In our experience, both preoperative lymphoscintigraphy and intraoperative histologic evaluation add useful information to the procedure.