Wound healing and catheter thrombosis after implantable venous access device placement in 266 breast cancers treated with bevacizumab therapy.

The aim of this study was to determine, in a population with metastatic breast cancer treated with bevacizumab therapy, the incidence of wound dehiscence after placement of an implantable venous access device (VAD) and to study the risk of catheter thrombosis. This study enrolled all VADs placed by 14 anesthetists between 1 January 2007 and 31 December 2009: 273 VADs in patients treated with bevacizumab therapy and 4196 VADs in patients not treated with bevacizumab therapy. In the bevacizumab therapy group, 13 cases of wound dehiscence occurred in 12 patients requiring removal of the VAD (4.76%). All cases of dehiscence occurred when bevacizumab therapy was initiated less than 7 days after VAD placement. Bevacizumab therapy was initiated less than 7 days after VAD placement in 150 cases (13 of 150: 8.6%). The risk of dehiscence was the same from 0 to 7 days. In parallel, the VAD wound dehiscence rate in patients not receiving bevacizumab therapy was eight of 4197 cases (0.19%) (Fisher's test significant, P<0.001). No risk factors of dehiscence were identified: anesthetists, learning curves, and irradiated patients. VAD thrombosis occurred in four patients (1.5%). In parallel, VAD thrombosis occurred in 51 of 4197 patients (1.2%) not receiving bevacizumab therapy (Fisher's test not significant; P=0.43). Bevacizumab therapy was permanently discontinued in five patients related to wound dehiscence and in one patient due to extensive skin necrosis. These data suggest the need to observe an interval of at least 7 days between VAD placement and initiation of bevacizumab therapy to avoid the risk of a wound dehiscence requiring chest wall port explant. The risk of VAD thrombosis does not require any particular primary prevention.

Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature.

As tumours in BRCA1/2 mutation carriers might be more sensitive to radiation, we investigated after long-term follow-up whether mutation status influenced the rate of ipsilateral and contralateral breast cancers after breast-conserving treatment (BCT). BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer who had undergone BCT and radiotherapy. Patients were matched to 261 controls with sporadic breast cancer according to age at diagnosis and year of treatment. Controls were followed up for at least as long as the interval between diagnosis and genetic screening in familial cases. Rates of ipsilateral and contralateral cancer between groups were compared by the log-rank test. The BRCA1/2 mutations occurred in 20.6% of tested patients. Tumours in mutation carriers were more likely to be grade III (P < 10(-4)) and oestrogen receptor negative (P = 0.005) than in non-carriers and controls. Overall median follow-up was 161 months. There was no significant difference in ipsilateral tumours between mutation carriers, non-carriers and controls (P = 0.13). On multivariate analysis, age was the most significant predictor for ipsilateral recurrence (P < 10(-3)). The rate of contralateral cancer was significantly higher in familial cases: 40.7% (mutation carriers), 20% (non-carriers), and 11% (controls) (P < 10(-4)). After 13.4 years of follow-up, the rate of ipsilateral tumours was no higher in mutation carriers than in non-carriers or controls. As tumours in BRCA1/2 mutation carriers might be more sensitive to radiation, BCT is a possible treatment option.

Management of operable invasive breast cancer in women over the age of 70: long-term results of a large-scale single-institution experience.

BACKGROUND: The treatment of choice for elderly women with breast cancer remains controversial. This retrospective analysis of a cohort from a single institution was designed to evaluate whether such patients are really undertreated because of their age and to reappraise their usual management. METHODS: The characteristics of 538 patients aged > or = 70 years with operable breast cancer, treated between 1995 and 1999, were retrospectively analyzed comparing patients aged 70 to 75 years (group I, n = 288), 75 to 80 years (group II, n = 156), and > or = 80 years (group III, n = 94). Cause-specific survival, distant recurrence-free interval, and local control were estimated by the Kaplan-Meier method and compared by log rank test. Multivariate analysis used Cox regression. RESULTS: In group III, tumors were more frequently T2 than T1 (P < 0.0001) and estrogen receptor negative (P = 0.045) than in groups I and II. Surgery was performed in 94.6% of patients, breast-conserving in 72.1% (62% in group III; P = 0.0015) with axillary dissection in 89.2% (77% in group III; P = 0.0015); 100% received radiotherapy after lumpectomy (hypofractionated in 63% of group III; P < 0.0001). Adjuvant hormone therapy and chemotherapy were administered to 57 and 3.7% of patients, respectively. At 7 years, no difference in the three groups was observed for cause-specific survival (91% for group I, 89% for group II, 86% for group III) distant recurrence-free interval, and local control (>90%). CONCLUSIONS: Elderly patients with operable breast cancer who are completely and correctly treated with realistic treatment options that are based on surgery and adjuvant radiotherapy have a similar chance of being cured as younger patients.

Pathologic response rate after concomitant neo-adjuvant radiotherapy and chemotherapy for adenocarcinoma of the uterine cervix: a retrospective multicentric study.

INTRODUCTION: Exclusive chemoradiotherapy (including brachytherapy) is the current standard of care for locoregionally advanced cervical cancer. The aim of the present study was to evaluate the responsiveness and to identify factors predicting the response to concomitant chemoradiotherapy before surgery in cervical adenocarcinoma. METHODS: A multicentric retrospective study was done in 9 French centers. A total of 54 women with cervical adenocarcinoma stage IB2 to IIIB who had undergone concurrent chemoradiation therapy followed by surgical treatment were included. The patients were stratified by histopathologic response after concomitant chemoradiotherapy (lesions smaller than 1 cm or larger). RESULTS: The median (SD) age at diagnosis was 44.2 (12.4) years (range, 19.3-77 years). The median (SD) follow-up duration was 30.9 (36.5) months (range, 4.1-17 years). After clinical evaluation, the mean (SD) tumor size was 5 (1.2) cm (range, 2-7 cm).The patients achieved a clinical complete response after concurrent chemoradiation in 18 cases (33.5%). Pathologic residual tumor was noted in 36 cases (67%); tumors smaller than 1 cm were found in 18 cases (33.5%), and lesions greater than 1 cm were observed in 18 cases (33.5%). Factors being associated with a significant decreased sensitivity to neoadjuvant chemoradiotherapy were the following: menopause (P = 0.012), parametrial invasion (P < 0.001), lymphovascular space invasion (P = 0.003), and mucinous subtype (P = 0.001). CONCLUSIONS: Identification of predictive markers associated with incomplete response to neoadjuvant chemoradiotherapy in cervical adenocarcinoma may prove clinically useful and implement an individualized treatment plan.

Different outcome of invasive cervical cancer associated with high-risk versus intermediate-risk HPV genotype.

Human papillomavirus (HPV) DNA sequences are associated with the large majority of invasive cervical carcinoma but the role of specific genotype(s) in the outcome of the disease is still debated. To determine the viral epidemiology in the French population of patients and the prognostic value of HPV genotypes in cervical cancer, we performed a retrospective study in 515 patients treated in our Institution from 1985 to 2005. Ninety-six percent of the cases were found associated with HPV DNA whereas 4% remained HPV negative. High-risk HPV 16/18 genotypes were found in 70% of the cases. HPV 18 was more frequently associated with adenocarcinoma (40.6%) than HPV 16 (10.4%) and found in tumours developed in younger women (mean age, 45.8 years) than HPV 16 (48.3 years) or other HPV types (53.6 years). In multivariate analysis, node involvement (p < 0.0001), parametria invasion (p = 0.009), tumour size (p = 0.01) and HPV status (p = 0.02) were associated with disease-free survival (median follow-up 95 months). Disease outcome was better in tumours associated with intermediate risk HPV types (HPV 31, 33, 35, 39, 52, 53, 58, 59, 73) than in tumours with high oncogenic types (HPV 16, 18, 45) (p = 0.03). Node status and tumour size remained prognostic factor for overall survival. Our data show that HPV genotype is one of the biological factors associated with the outcome of cervical cancer. One third of invasive carcinoma were not associated with HPV 16/18, indicating that the screening for cervical neoplasia should be maintained after prophylactic vaccination against these HPV genotypes.

A novel treatment for postoperative mondor's disease: manual axial distraction.

Mondor's disease is an uncommon complication of breast and axillary surgery. Although self-limiting, the subcutaneous cords may be both painful and functionally limiting for the patient. Numerous pharmacologic approaches have been tried, but without widespread success, and we wished to evaluate the non-invasive technique of manual axial distraction in such patients. Thirty consecutive patients with axillary Mondor's disease following surgery were treated solely with this technique by the senior author (RJS) over a 24-month period. Mean age was 45 years (range 32-72) with 27 having undergone formal axillary dissection and three sentinel node biopsy. 25 (83.3%) were successfully treated with a single procedure, three (10%) with two and two (6.7%) with three procedures. we present the initial results of the novel technique of manual axial distraction that has been found to be efficacious and without adverse effect. It provides a rapid and definitive cure in postoperative Mondor's disease.

A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer.

INTRODUCTION: Several gene expression signatures have been proposed and demonstrated to be predictive of outcome in breast cancer. In the present article we address the following issues: Do these signatures perform similarly? Are there (common) molecular processes reported by these signatures? Can better prognostic predictors be constructed based on these identified molecular processes? METHODS: We performed a comprehensive analysis of the performance of nine gene expression signatures on seven different breast cancer datasets. To better characterize the functional processes associated with these signatures, we enlarged each signature by including all probes with a significant correlation to at least one of the genes in the original signature. The enrichment of functional groups was assessed using four ontology databases. RESULTS: The classification performance of the nine gene expression signatures is very similar in terms of assigning a sample to either a poor outcome group or a good outcome group. Nevertheless the concordance in classification at the sample level is low, with only 50% of the breast cancer samples classified in the same outcome group by all classifiers. The predictive accuracy decreases with the number of poor outcome assignments given to a sample. The best classification performance was obtained for the group of patients with only good outcome assignments. Enrichment analysis of the enlarged signatures revealed 11 functional modules with prognostic ability. The combination of the RNA-splicing and immune modules resulted in a classifier with high prognostic performance on an independent validation set. CONCLUSIONS: The study revealed that the nine signatures perform similarly but exhibit a large degree of discordance in prognostic group assignment. Functional analyses indicate that proliferation is a common cellular process, but that other functional categories are also enriched and show independent prognostic ability. We provide new evidence of the potentially promising prognostic impact of immunity and RNA-splicing processes in breast cancer.

[Sentinel node identification in breast cancer: logistic aspects]. / Identification du ganglion sentinelle dans le cancer du sein : aspects logistiques.

Sentinel node identification has gained its place in early breast cancer surgical management before the results of prospective randomized trials. Published results can be explained by teams configurations and technical aspects can create some confusion in results analysis. Logistic aspects confers a specificity for each team. Sentinel node technique should be reserved to experienced treatment center where it can be utilized routinely.

Oncoplastic surgery in breast conservation: a prospective evaluation of the patients, techniques, and oncologic outcomes.

BACKGROUND: The oncologic efficacy of breast-conserving therapies has been established in recent decades. Oncoplastic breast surgery (OBS), as a leap forward in breast conservation, offers concomitant techniques of oncologic and plastic surgeries that grant better esthetic results. The outcomes of our oncoplastic surgeries from 2007 to 2012 are reported. METHODS: A series of 258 cases with breast masses (18 benign and 240 carcinomas) were operated on by OBS techniques and prospectively followed. Neoadjuvant and adjuvant oncologic treatments were also delivered as indicated. RESULTS: Free margins were obtained in 95% of cancer patients. During the 26 months of follow-up, local recurrence happened in 7 (2.9%) patients, of which 1 underwent oncologic therapies and 6 underwent completion mastectomy. Complications postponed adjuvant therapies in 3 (1.2%) patients. Postsurgically, metastases were diagnosed in 8 (3.3%) patients. Two patients (.8%) died of cancer. CONCLUSIONS: Outcomes of OBS are oncologically acceptable with low frequencies of positive margins and recurrence, while cosmetic results are much improved by OBS.

Breast and ovarian cancer risk management in a French cohort of 158 women carrying a BRCA1 or BRCA2 germline mutation: patient choices and outcome.

Description of the various modalities of breast and ovarian cancer risk management, patient choices and their outcome in a single-center cohort of 158 unaffected women carrying a BRCA1 or BRCA2 germline mutation. Between 1998 and 2009, 158 unaffected women carrying a BRCA1 or BRCA2 gene mutation were prospectively followed. The following variables were studied: general and gynecological characteristics, data concerning any prophylactic procedures, and data concerning the outcome of these patients. Median age at inclusion was 37 years and median follow-up was 54 months. Among the 156 women who received systematic information about prophylactic mastectomy, 5.3 % decided to undergo surgery within 36 months after disclosure of genetic results. Prophylactic salpingo-oophorectomy was performed in 68 women. Among women in whom follow-up started between the ages of 40 and 50 years, prophylactic salpingo-oophorectomy was performed, within 24 months after start of follow-up, in 83.7 and 52 % of women with BRCA1 and BRCA2 mutations, respectively. Twenty four women developed breast cancer. Ovarian cancer was detected during prophylactic salpingo-oophorectomy in two women (2.9 %). In this cohort of French women carrying BRCA1/2 mutations, prophylactic mastectomy was a rarely used option. However, good compliance with prophylactic salpingo-oophorectomy was observed. This study confirms the high breast cancer risk in these women.

Gastric metastasis of breast cancer: a single centre retrospective study.

BACKGROUND: Digestive metastasis of breast cancer are rare but when they do occur the stomach is one of the commoner sites. AIM: To describe the clinical, endoscopic, pathological features and treatment. METHODS: 35 cases of gastric metastasis were identified retrospectively between 1980 and 2008. RESULTS: The location of the gastric metastasis was fundus (n=15, 43%), antrum (n=15, 43%) or both (n=5, 14%). The histological subtype of primary breast cancer was invasive lobular carcinoma in 34 patients (97%). Hormonal receptors were positive in 19 out of 24 cases (79%), two out of 22 analysed were HER2 positive (9%). There were 16 (46%) patients with peritoneal carcinosis. The treatment was chemotherapy (n=13, 37%), hormonotherapy (n=2, 6%) or both (n=13, 37%). The 2-year survival rate after gastric metastasis diagnosis was 53% with a median follow up of 31 months [7-84 months]. CONCLUSION: Ninety-seven percent of gastric metastasis from breast cancers are derived from invasive lobular carcinoma. Seventy-nine percent of these are HER+ and comparison with the original histopathological slides of primary breast carcinoma should be performed to differentiate gastric metastasis from primary gastric carcinoma. Peritoneal carcinomatosis accompanied gastric metastasis in almost half the cases in this series and treatment was generally chemotherapy.

The molecular subtype classification is a determinant of sentinel node positivity in early breast carcinoma.

INTRODUCTION: Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy. MATERIALS AND METHODS: Our dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype. RESULTS: The interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031) of positive sentinel node biopsy than the ER status by itself (p = 0.016). A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72) and calibration (HL p = 0.28/0.05/0.11) in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated. DISCUSSION: We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.

Oncoplastic breast surgery for cancer: analysis of 540 consecutive cases [outcomes article].

BACKGROUND: Synchronous plastic and oncological surgery is undertaken to improve the security of excision margins and yield high-quality aesthetic outcomes when conventional breast-conserving therapy either anticipates poor results or is not possible. METHODS: A total of 540 consecutive patients underwent primary oncoplastic breast surgery for cancer with high tumor-to-breast volume ratios and locations precluding a good aesthetic result with simple tumor excision. A variety of techniques were employed at the Institut Curie between 1986 and 2007, and aesthetic outcomes were assessed on a five-point scale from 1 (excellent) to 5 (poor). RESULTS: The median age was 52 years (range, 28 to 90 years), and median follow-up was 49 months (6 to 262 months). Median tumor size was 29.1 mm (range, 4 to 100 mm), with most patients (72.3 percent) having a brassiere cup size of B or C. Close or involved margins occurred in 18.9 percent, with mastectomy being necessary in 9.4 percent. A satisfactory aesthetic outcome (ratings of 1 to 3) at 5 years was obtained in 90.3 percent. Five-year overall and distant disease-free survival rates were 92.9 and 87.9 percent, respectively, with local recurrence in 6.8 percent. CONCLUSIONS: With local recurrence and survival rates similar to those for breast-conserving therapy, this series confirms the safety of oncoplastic breast surgery for tumors both high in volume and difficult in location. Highly satisfactory cosmetic outcomes extend the indications for conservative surgery, further reduce the mastectomy rate, and limit adverse aesthetic sequelae.

Management of the post-breast-conserving therapy defect: extended follow-up and reclassification.

BACKGROUND: Suboptimal aesthetic outcomes after conservative therapy for breast cancer are not uncommon, with reported rates up to 30 percent, of which 5 percent may be considered severe. With radiotherapy being an essential component of breast-conserving therapy, surgical correction of deformities is challenging, and guidance as to reparative technique selection is currently limited. METHODS: One hundred forty-one patients have undergone surgical correction of breast-conserving therapy-induced deformity since its inception at our institution in 1991. This consecutive series has been analyzed with respect to surgical procedure, complications, revisional surgery, and aesthetic outcome (with a five-point scale) to July of 2008. RESULTS: The overall aesthetic result was considered to be at least satisfactory in 94.5 percent at 1 year and in 88.8 percent at 5 years. Secondary surgery was required in 19.1 percent and a third procedure was required in 6.4 percent. Complications were encountered in 14.2 percent. A classification into five grades of deformity was found to be practical and effective for surgical planning. CONCLUSIONS: Reparative surgery for aesthetic deformity in scarred and irradiated breasts is able to produce satisfactory aesthetic results; however, revisional surgery and complications are not inconsiderable, and the authors hope the new classification based on their long-term experience will provide practical guidance for surgical planning to other surgeons encountering such patients.

Breast-conserving treatment in the elderly: long-term results of adjuvant hypofractionated and normofractionated radiotherapy.

PURPOSE: To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT). METHODS AND MATERIALS: Between 1995 and 1999, 367 women aged >or=70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed by a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients. RESULTS: A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively. CONCLUSION: According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results.

Ductal carcinoma in situ of the breast with close or focally involved margins following breast-conserving surgery: treatment with reexcision or radiotherapy with increased dosage.

PURPOSE: Following breast-conserving surgery for DCIS, reexcision before radiotherapy is recommended when margins are close or involved. We investigated whether an additional radiation dose could replace reexcision. METHODS: We selected 208 women with DCIS of the breast treated with breast-conserving surgery between 1992 and 2002 who had either close margins (< 2 mm) (89 pts) or focally (< 1 mm) or minimally (1-15 mm) involved margins (119 pts). Sixty-one patients (29%) underwent reexcision before irradiation and 147 patients (71%) received breast irradiation with boost, without reexcision. RESULTS: Median follow-up was 89 months. Median age was 53 years with 7 patients less than 41. Involved margins were less frequent in the non reexcision group than in the reexcised group (50% vs. 74%, p = 0.0019). All other clinical and histological features were comparable. Median whole-breast radiation dose was 50 Gy. Median total doses to the tumour bed were 67 Gy (range, 45-77) and 60 Gy (range, 46-74), respectively (p < 0.0001). Of the 61 reexcised patients, 56% had residual DCIS and 6% had invasive cancer. Six underwent a mastectomy for persistent margin involvement. Seven-year locoregional failure rates were 9.3% without, and 9.6% with reexcision (ns). No differences were observed when adjusting for margin status. CONCLUSION: In carefully selected patients with close (< 2 mm) or focally/minimally involved margins, reexcision may be avoided and satisfactory local control achieved by increasing the radiation dose to the tumour bed to at least 66 Gy. These results only apply to patients older than 40 and would need confirmation in independent series.

[Reduction mammoplasty in breast cancers of the lower quadrants]. / Traitement des cancers des quadrants inférieurs du sein par plastie mammaire bilatérale de réduction.

AIM: Evaluate bilateral reduction mammoplasty in the management of breast cancer in the lower quadrants. PATIENTS AND METHODS: 60 patients were operated on between 1992 and 2003 mean age: 53 years (34-75) by a double team, oncologic and plastic, during the same operative procedure for a cancer in the lower quadrants (T1-2, N0-1a, M0). Radiation therapy was delivered in every patient with a boost in 30% of them. RESULTS: Mean cancer size was 17,5 mm (5-20 m) with 10 N + patients. Mean weight of the lumpectomy was 220 g (80-900!). There was one local recurrence at three years. Cosmetic result was good in 75 % of the patients. Radiation side effects: fibrosis, induration, telangiectasias and vicious cicatrisation on the contro-lateral breast were responsible of the middle quality results. CONCLUSION: Bilateral reduction mammoplasty is a good technique for the management of cancers in the lower quadrants. A double team, with a good logistic organisation, gives a good oncoplastic result.