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Purpose: GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients., Methods: Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone., Results: From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3-17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed., Conclusion: In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

Background: Mastectomy with immediate breast reconstruction (IBR) is a surgical strategy in breast cancer when breast-conserving surgery is not an option. There is a lack of evidence showing an advantage of mastectomy plus IBR over mastectomy alone on health-related quality of life (QoL)., Methods: A large prospective multicentre survey, STIC-RMI (support of innovative and expensive techniques - immediate breast reconstruction), was undertaken to study the changes in QoL in patients treated by mastectomy with or without IBR. Patients were recruited between 2007 and 2009. European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 instruments were used to assess QoL before operation, and at 6 and 12 months after surgery. A propensity score was used to compare QoL between mastectomy alone and mastectomy plus IBR, with limited bias., Results: A total of 595 patients were included from 22 French academic hospitals, of whom 407 (68·4 per cent) underwent IBR. One-year data were available for 71·1 per cent of patients. Factors associated with IBR were age, histological tumour type, palpable nodes and an attempt at breast-conserving surgery. At inclusion, QoL was significantly better in the IBR group (P < 0·001) and there was no significant change in either group during 1 year compared with baseline. Results for the QLQ-BR23 functional dimension varied according to propensity score quartiles; IBR had no influence in the lowest quartile. In the upper quartiles, QoL increased slightly over the year among patients who had IBR, whereas it decreased among those who had mastectomy alone (P = 0·037). Satisfaction with the cosmetic outcome strongly influenced QoL, especially in upper quartiles (P < 0·001). However, an unsatisfactory outcome after IBR was still considered a better condition than simple mastectomy., Conclusion: The QoL benefit provided by IBR depends on patients' life status at inclusion; young active women with an in situ tumour are more likely to preserve their QoL after IBR., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Aim: Sentinel lymph node (SLN) biopsy was recently recommended after prior breast tumour surgery and lymphadenectomy is not the gold standard anymore for nodal staging after a lesion's removal. The purpose of our study was to evaluate the good practices of use of SLN biopsy in this context., Patients and Methods: From 2006 to 2012, 138 patients having undergone a surgical biopsy without prior diagnosis of an invasive carcinoma with a definitive histological analysis in favour of this diagnosis were included in a prospective observational multicentric study. Each patient had a nodal staging following SLN biopsy with subsequent systematic lymphadenectomy., Results: The detection rate of SLN was 85.5%. The average number of SLNs found was 1.9. The relative detection failure risk rate was multiplied by 4 in the event of an interval of less than 36 days between the SLN biopsy and the previous breast surgery, and by 9 in the event of using a single-tracer detection method. The false negative rate was 6.25%. The prevalence of metastatic axillary node involvement was 11.6%. In 69% of cases only the SLN was metastatic. The post-operative seroma rate was 19.5%., Conclusion: Previous conservative breast tumour surgery does not affect the accuracy of the SLN biopsy. A sufficient interval of greater than 36 days between the two operations could allow to improve the SLN detection rate, although further studies are needed to validate this statement., Clinical Trial Registration Number: NCT00293865., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Aromatase inhibitor (AI) therapy is associated with musculoskeletal (MS) toxicity, which adversely affects quality of life and therapy adherence. Our objective was to evaluate whether genetic variants may predict endocrine therapy-related MS pain and hot flashes in a prospective observational cohort study., Patients & Methods: 254 early breast cancer patients starting AI (n = 159) or tamoxifen therapy (n = 95) were included in this genetic biomarker study. MS and vasomotor symptoms were assessed at baseline and after 3, 6 and 12 months of therapy. AI-induced MS pain was defined as an increase in arthralgia or myalgia relative to baseline. Single nucleotide polymorphisms (SNP) in candidate genes involved in oestrogen signalling or previously associated with AI-related MS pain or oestrogen levels were selected., Results: Overall, 13 SNPs in CYP19, CYP17, osteoprotegerin (OPG) and oestrogen receptor 1 exhibited an allele frequency >0.05 and were included in the analysis. Patients carrying the G allele of rs2073618 in OPG experienced significantly more AI-induced MS toxicity compared to the wildtype allele, after correction for multiple testing (P = 0.046). Furthermore, this SNP was associated with severity of pain (P = 0.018). No association was found with regard to the other SNPs, both in AI and tamoxifen-treated patients. Neither could an association with vasomotor symptoms be demonstrated., Conclusion: The SNP rs2073618 in OPG is associated with an increased risk of MS symptoms and pain with AI therapy, which has not been reported previously. Validation of this finding in larger cohorts and further functional studies are required., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Aromatase inhibitors (AIs) frequently induce or enhance musculoskeletal problems (AI-induced musculoskeletal syndrome (AIMSS)) which sometimes are debilitating. Apart from low oestrogen levels, underlying mechanisms are unknown and likely multiple. We previously hypothesised a role for the growth hormone/insulin like growth factor-I (IGF-I) axis. Here, we report the effect of tamoxifen and AI on IGF-I, IGF binding protein-3 (IGFBP-3) and oestrogen levels from a prospective study., Materials and Methods: Postmenopausal women with an early breast cancer scheduled to start adjuvant endocrine therapy with an AI or tamoxifen were recruited. A rheumatologic questionnaire was completed and serum was collected for assessment of IGF-I, IGFBP-3 and oestrogen levels. Re-evaluation was done after 3, 6 and 1 2months of therapy., Results: 84 patients started on tamoxifen (n=42) or an AI (n=42). 66% of the latter group experienced worsening of pre-existing or de novo complaints in joint and/or muscle, compared to 29% of tamoxifen-treated patients. AI therapy resulted in elevated IGF-I levels with a statistically significant increase at 6months (p=0.0088), whereas tamoxifen users were characterised by a decrease in IGF-I levels at all follow-up times (p<0.0004). No effect on IGFBP-3 was seen in the latter group. AI-users, however, showed decreased IGFBP-3 levels at 12 months (p=0.0467). AIMSS was characterised by a decrease in IGFBP-3 levels (p=0.0007) and a trend towards increased IGF-I/IGFBP-3 ratio (p=0.0710)., Conclusion: These findings provide preliminary evidence that AI-induced musculoskeletal symptoms are associated with changes in the growth hormone (GH)/IGF-I axis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aromatase inhibitor (AI) therapy for estrogen receptor-positive breast cancer is known to induce or enhance musculoskeletal problems. We have previously reported that loss of grip strength is more pronounced in AI-users with extremes in BMI. We here report results from a larger prospective study. Postmenopausal early breast cancer patients scheduled to start AI or tamoxifen therapy were recruited. A functional assessment grip strength test was performed at baseline, 3, 6, and 12 months of therapy. BMI was assessed, and a rheumatologic questionnaire was completed at each visit. 188 patients on an AI and 104 patients on tamoxifen were enrolled. 74 % of AI-users reported new/worsened musculoskeletal complaints compared with 37 % in the tamoxifen group. This was translated in a larger grip strength decrease in patients experiencing AI-induced pain opposed to patients without new/worsened complaints (p = 0.0002). 15 % of AI-users discontinued therapy due to musculoskeletal symptoms, who were characterized by a larger grip strength reduction versus adherent patients (p = 0.0107). Young age (p = 0.0135), taxane-based chemotherapy (p = 0.0223), and baseline VAS score >4 (p = 0.0155) were predictors for AI-related musculoskeletal pain. In addition, a quadratic trend of BMI with grip strength change (p = 0.0090) and probability of discontinuation was observed (p = 0.0424). Musculoskeletal events were a substantial problem in AI-treated patients and an important reason for treatment discontinuation. The decrease in grip strength was larger in AI- than in tamoxifen-users, with a more pronounced change in symptomatic patients. The inverse relationship between BMI extremes and grip strength change was confirmed in this large group of AI-patients.

Introduction: Breast carcinomas are the most frequent form of cancer in French women. Following a total mastectomy, only an estimated 25% of patients wish to undergo breast reconstruction. After mammary volume reconstitution, the plastic surgeon often attempts to harmonize the two breasts by carrying out contralateral reduction mammaplasty (CRM). In the literature, the incidence of occult contralateral carcinomas incidentally discovered in surgical specimens ranges from 1.12 to 4.5%. The main objective of this study was to evaluate occurrence of carcinoma in the CRM specimens in the framework of a breast reconstruction operation. The secondary objective was to determine the consequences of the incidentally discovered carcinoma in the contralateral breast., Material and Methods: This was a 6-year, bicentric, retrospective study involving women having undergone breast cancer surgery who later underwent contralateral reduction mammaplasty (CRM), that is to say reconstruction aimed at harmonization of the two breasts., Results: Three hundred and nineteen patients were included in the study. Mean age during the CRM was 55years (29-79). Mean weight of the surgical specimens was 323grams (12-2500). Incidence of occult carcinomas found in the specimens was 0.94% (3 patients). The mean age for these 3 cases was 58years (47-64). All 3 patients had superior pedicle mammaplasty. One of the patients benefited from monobloc resection with orientation of the surgical specimen. In the other 2 cases, there existed 3 surgical resection specimens; in one case, they were oriented; in the other, they were not. In all 3 cases, the histological findings were unifocal ductal carcinomas in situ (DCIS). Mean tumor size was 5.7mm (3-9). Only the patient having had monobloc resection with orientation of the specimen underwent salvage surgery, which consisted in partial mastectomy, otherwise known as secondary lumpectomy. Adjuvant radiotherapy was administered to all of the patients. After 17months of mean follow-up (12-22), no recurrence was found in any of the three cases., Conclusion: Incidence of occult contralateral breast carcinomas after symmetrization CRM approximates 1%. Our observations are in agreement with the data in the literature. Incidence is greater than in mammaplasty carried out for esthetic or functional reasons; this is probably due to the higher age and the previous breast cancer history of the breast reconstruction population. Monobloc resection and orientation of the surgical specimens with surgeon's knots facilitate precise pinpointing of the occult carcinoma. A secondary lumpectomy may take place when margins of excision are invaded or inadequate., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Aromatase inhibitors (AIs) frequently lead to the AI-induced musculoskeletal syndrome (AIMSS). Looking into its pathophysiology, 6 months of AI therapy thickens the tendon sheath with intra-articular fluid (IAF) retention and loss of grip strength. We here report 24-month follow-up data., Patients and Methods: A prospective cohort study of 33 postmenopausal breast cancer patients received adjuvant endocrine therapy; 27 received an AI and 6 received tamoxifen. At baseline, 6 and 24 months patients had a rheumatologic examination, including a grip strength test, and magnetic resonance imaging of both hands and wrists. The primary end point was tenosynovial changes; secondary end points were changes in morning stiffness, grip strength and IAF., Results: Twenty-three AI and 5 tamoxifen patients completed all investigations. Between month 6 and 24, IAF further increased in AI users (P = 0.04) but not in tamoxifen users, and grip strength further decreased in both groups. The worsened tenosynovial changes were strongly correlated with a decrease in grip strength. At 24 months, morning stiffness continued to be present in over a third of AI users., Conclusion: AIMSS represents a substantial problem in breast cancer patients. It is associated with tenosynovial changes, IAF retention, joint stiffness and loss of grip strength that do not improve with prolonged use.

Background: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy., Materials and Methods: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models., Results: Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8)., Conclusion: In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings.

Background: Our preliminary results showed that tenosynovial changes and decrease in grip strength are associated with the aromatase inhibitor-induced musculoskeletal syndrome (AIMSS). Here, we report the final results and assess the relationship between grip strength and body mass index (BMI)., Patients and Methods: We conducted a prospective study including postmenopausal early breast cancer patients receiving either an aromatase inhibitor (AI) or tamoxifen. Primary end point was change from baseline in tenosynovial abnormalities. Secondary end points were changes from baseline in morning stiffness, intra-articular fluid and grip strength and its association with BMI., Results: After 6 months of therapy, 74% [95% confidence interval (CI) 51% to 89%] of AI-treated patients had worsened tenosynovial abnormalities, 56% (95% CI 34% to 75%) had increased intra-articular fluid, and 22% (95% CI 9% to 45%) had increased morning stiffness. Grip strength decreased 8% for the left hand (95% CI 2% to 21%) and 11% for the right (95% CI 4% to 17%). Regression analysis suggested that grip strength decreased more for subjects with high or with low BMI., Conclusions: AIMSS is characterized by tenosynovial changes, intra-articular fluid and morning stiffness. We hypothesize that the quadratic association between BMI and loss of grip strength reflects AI-induced changes on the endocrine control of the growth hormone insulin-like growth factor-I pathway.

Objective: Arthralgia, skeletal and muscle pain have been reported in postmenopausal women under treatment with third generation aromatase inhibitors (AIs). However, the pathogenesis and anatomic correlate of musculoskeletal pains have not been thoroughly evaluated. Moreover, the impact of AI-induced musculoskeletal symptoms on normal daily functioning needs to be further explored., Patients and Methods: We examined 12 consecutive non-metastatic breast cancer patients who reported severe musculoskeletal pain under a third generation AI; 11 were on letrozole and 1 on exemestane. Clinical rheumatological examination and serum biochemistry were performed. Radiological evaluation of the hand/wrist joints were performed using ultrasound (US) and/or magnetic resonance imaging (MRI)., Results: The most common reported symptom was severe early morning stiffness and hand/wrist pain causing impaired ability to completely close/stretch the hand/fingers and to perform daily activities and work-related skills. Six patients had to discontinue treatment due to severe symptoms. Trigger finger and carpal tunnel syndrome were the most frequently reported clinical signs. US showed fluid in the tendon sheath surrounding the digital flexor tendons. On MRI, an enhancement and thickening of the tendon sheath was a constant finding in all 12 patients., Conclusions: Musculoskeletal pains in breast cancer patients under third generation AIs can be severe, debilitating, and can limit compliance. Characteristic tenosynovial, and in some patients joint changes on US and MRI were observed in this series and have not been reported before.

Purpose: To retrospectively assess the efficacy of post-mastectomy re-irradiation for local relapse of breast cancer., Patients and Methods: Twenty patients, initially treated by conservative surgery and radiotherapy (50 Gy in 25 fractions over 5 weeks) were treated from 1998 to 2001 for a local relapse by salvage mastectomy and re-irradiation (either electron or photon beams). Mean age was 53 years (31-71). Reasons for re-irradiation were that the local relapses were inflammatory (4 pts), multifocal (5 pts), cutaneous (5 pts), involved the nipple (3 pts) or because the surgical margins (either muscle or skin) were involved (3 pts). The median dose of re-irradiation was 45 Gy (33-65) in 15 fractions over 33 days. Mean follow-up was 48 months (5-97)., Results: Fifteen patients remained free of a second local recurrence and 10 were still alive, without metastasis. Neither the dose of re-irradiation nor the irradiated surfaces were prognostic factors of local control (P = 0.877 and P = 0.424). Five patients developed radiation-induced pneumonitis without functional respiratory impairment. The incidence of pneumonitis seemed to be related to the biological dose of re-irradiation (P = 0.037). Other late complications occurred such as pigmentation changes (12 pts), telangiectasia (8 pts), chondritis (2 pts), parietal fibrosis (7 pts), rib fractures (4 pts), severe pain (11 pts) and lymphedema (2 pts). The increase in biological equivalent dose was highly statistically linked with the occurrence of disabling pain (P = 0.0123)., Conclusion: Parietal re-irradiation achieves good and lasting local control with an acceptable rate of acute complications but with a risk of disabling late sequelae such as severe pain.

Purpose: Breast cancer rarely occurs in very young women, its diagnosis and management could sometimes be difficult. Our aim is to analyse the epidemiological and clinicopathological features of a group of very young women and especially to evaluate the results of therapeutic strategy., Methods: We report a retrospective study conducted at the department of radiotherapy in Alexis-Vautrin Centre, concerning 30 patients aged < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between 1986 and 2001., Results: Six patients had familial history of breast cancer. Palpable tumor was found in 90% of cases, the average size was 3.5 cm. Eleven patients presented with stage I, 11 presented with stage II, 6 presented with stage III and 2 presented with stage IV. Five cancers were diagnosed after pregnancy (average tumor size = 5.8 cm). Eleven patients received neoadjuvant chemotherapy and 23 (82%) of 28 operable cases of invasive malignancy underwent breast conservative surgery (BCS). We found an invasive ductal carcinoma with grade III in 13/27 cases and a nodal involvement in a half of cases, 11 patients of 26 had no expression of oestrogen receptor. The average follow-up was 5 years: six patients (20%) recurred locally (all of them were initially treated by BCS), four patients developed a contralateral breast cancer and three developed a second malignancy. Ten patients died of their metastatic disease. The 5-year overall survival rate was 78%., Conclusion: Our results are consistent with those of the published reports and suggest that very young women with breast cancer have a poorer prognosis compared with the older ones. They should receive, according to their prognostic factors, an appropriate regional, systemic and hormonal therapy.

Ectopic breast tissue usually develops along the mammary ridge. The incidence of this anomaly has been reported as high as 6%. Malignant development is rare. A case of carcinoma of aberrant breast tissue, located in the axilla is described. Mammographies of the ectopic breast performed few years before the diagnosis of carcinoma are presented and also those done for the diagnosis of the tumor. A literature study was performed on carcinoma and ectopic breast tissue. Considering high frequence of node involvements for these cases, the optimal therapeutic strategies are discussed.

Because of its high incidence and the high number of deaths induced, breast cancers in elderly women is a major health problem. The diagnosis is often clinical and the tumors are often at advanced stage with many initial metastases due to some neglect. Breast cancer in elderly women has no specific radiological form and is more often infiltrating ductal carcinoma of SBR grade I. Hormonal receptors are generally higher in elderly than in young women. Surgery of breast cancers with equal anesthetic risks factors does not induce more complications in elderly women than in the general population. In 12% of cases, an associated pathology influences the decision (degradation of the respiratory or cardiovascular function or reduction of the renal function). Between 70 and 80 years, provided that life expectancy is compatible with radiotherapy, corollary to conservative treatments in the present state of our knowledge for tumors under 3 to 4 cm, there is an alternative between radiosurgical conservative treatment and modified mastectomy associated with axillary dissection. In case of bulky tumors (> 3 to 4 cm) and failure of the hormonal treatment or impossibility to perform a complementary radiotherapy treatment (for instance, senile dementia), of axillary node involvement, a fortiori if the tumor has no hormonal receptors, the modified mastectomy with axillary dissection remains the therapeutic standard. In case of bulky tumor, the hormonal status can be used to induce the patient to accept an operation and, if necessary, to perform a conservative surgery. However, despite hormonosensitivity of breast cancer, a tumoral progression after a mean duration of hormonosensitivity of 25 months is to be expected in 93% of the cases, included 25% in whom a complete response to hormonotherapy was observed. A fractionated irradiation delivering 2 Gy per fraction and 5 fractions per week with a total number of sessions of 25 gives better esthetical results. This optimal treatment lasts 5 weeks and the patients often get tired since they are old and their radiotherapy centre is far from their house. Therefore hypofractionated treatment (once a week) should be proposed. The adjuvant medical treatment of reference for menopausal women is hormonotherapy by tamoxifen. Breast cancer in elderly women reduces life expectancy at 5 years by 50%; the theoretical therapeutic indications are the same as for young women, but their application is adapted to the patient. It would be dangerous and illusive to undertreat such a disease when the life expectancy is longer than 3 years.