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Background: The impact of some hasty medical decision made during the first wave of the Coronavirus Disease 2019 (COVID-19) remains unknown. We have evaluated the consequences of one of these precautionary measures: the withdrawal of the cyclin D-dependent kinases 4/6 inhibitor (CDK4/6i) in patients whose metastatic disease was controlled by a combination of endocrine treatment and CDK 4/6i., Method: This study was noninterventional, retrospective, multicentric, and included 60 patients with HR+ HER2- metastatic disease. Their disease was controlled with the combination of endocrine treatment and CDK 4/6i. The CDK 4/6i was stopped for two months during the first COVID-19 outbreak. A univariate analysis was performed to assess the risk factors associated with disease progression., Results: During this therapeutic break, 22 (37 %) patients had a radiological and/or clinical disease progression. Among them, the CDK 4/6i was re-introduced to 16 patients (n = 16/22; 73 %). A new line of treatment (chemotherapy or targeted therapy) was initiated due to the rapid symptomatic tumor progression in four patients (n = 4/22; 18 %). Two patients (n = 2/22) died in visceral crisis before another anti-tumoral treatment was introduced. In univariate analysis, the presence of liver metastases increased the risk of metastatic disease progression during the withdrawal of the CDK 4/6 (OR = 6.6; 95 % CI 1.87-23.22; P= .0033)., Conclusion: Progression was observed in 37% of patients during the two-month treatment interruption of the CDK 4/6i. A prolonged CDK 4/6i treatment interruption in patients with clinical benefit on endocrine treatment does not seem to be a reasonable option in light of these results., Competing Interests: Disclosures T.P. reports grants from Pfizer, Novartis, AstraZeneca, Lilly, and Pierre Fabre, but which were unrelated to the submitted work. Other authors declare no conflicts of interest related to this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The potential effects of breast cancer (BC) on health-related quality of life (HRQoL) should be considered in clinical and policy decision-making, as the economic burden of BC management is currently assessed. In the last decades, time-to-HRQoL score deterioration (TTD) has been proposed as an approach to the analysis of longitudinal HRQoL in oncology. The main objectives of the current study were to investigate the evolution of the utility values in BC patients after diagnosis and during follow-ups and to evaluate the TTD in utility values among women in all stages of BC., Methods: Health-state utility values (HSUV) were assessed using the EuroQol 5-Dimension 3-Level at diagnosis, at the end of the first hospitalization and 3 and 6 months after the first hospitalization. For a given baseline score, HSUV was considered to have deteriorated if this score decreased by ≥ 0.08 points of the EQ-5D utility index score and ≥ 7 points of the EQ visual analogue scale. TTD curves were calculated using the Kaplan-Meier estimation method., Results: Overall 381 patients were enrolled between February 2006 and February 2008. The highest proportions of respondents at the baseline and all follow-ups reporting some and extreme problems were in pain discomfort and anxiety/depression dimensions; more than 80% of patients experienced a deterioration in EQ-5D utility index score and EQ VAS score with a median TTD of 3.15 months and 6.24 Months, respectively., Conclusions: BC patients undergoing therapy need psychological support to cope with their discomfort, pain, depression, anxiety, and fear during the process of diagnosis and treatment to improve their QoL., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: While several studies have documented fatigue during and after cancer treatment, long-term cancer survivor fatigue is underreported. In this study, we compare fatigue, quality of life (QoL), and anxiety between relapse-free cancer survivors 15 years after diagnosis and healthy controls., Methods: Cancer survivors (CS) were randomly selected from three large population-based cancer registries (Bas-Rhin, Calvados, and Doubs, France). Cancer-free controls were randomly selected from electoral lists with stratification on age group, residence area, and gender. All participants completed self-reported fatigue (MFI), QoL (EORTC QLQ-C30), and anxiety (STAI) questionnaires. Univariable and multivariable logistic regression were used to study the association between fatigue and cancer status, in three cancer subgroups: breast cancer (BC), cervical cancer (CC), and colorectal cancer (CRC)., Results: Two hundred sixty-three CS and 688 controls (125/275, 45/153, 93/260 CS/controls for BC, CC, and CRC respectively) were included. The mean age was 66 years. In multivariable analyses, CS had higher general and mental fatigue than controls p = 0.04 and p = 0.02, respectively. No difference in QoL was observed between CS and controls. CS were more anxious than controls (p < 0.01). Anxiety was associated with general fatigue (p < 0.0001) and mental fatigue (p < 0.0001)., Conclusion: Fifteen years after diagnosis, cancer survivors reported more general and mental fatigue compared with controls. Our results reinforce guidelines, identifying fatigue as a persistent symptom.

Breast cancer is the most common cancer among women. Localized breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. A monocenter historical cohort study including all women over 65 years of age treated between 2001 and 2016 with a taxane-based chemotherapy for localized breast cancer was carried out at the Paul Strauss Regional Comprehensive Cancer Center. All cases included were followed up for at least 2 years, deaths from causes unrelated to TIPN were excluded. We report on the frequency and risk factors and establish a prognostic score of persistent Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9% developed persistent TIPN of grade 2 and 3, respectively. Two patients died from complications of grade 3 TIPN. Risk factors of persistent grade 2 and higher neuropathy included age (P < .0001), body mass index (P < .0001), and diabetes (P = .0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (OR = 5.43; P < .0001). Patients presenting all four major risk factors had a 97.2% probability of developing long-term symptoms against 1.2% for patients showing no risk factor. We therefore identified 3 prognostic groups. TIPN is a frequent and sometimes severe persistent side effect of breast cancer treatment among elderly women with a major impact on health-related quality of life. Chemotherapy regimens without taxane could therefore be a valid option in elderly patients with neurotoxicity risk factors., (© 2020 Wiley Periodicals LLC.)

Women with breast cancer are increasingly being cured of the disease but fatigue remains the most frequently reported symptom. The aims of our study were to identify distinct trajectories in four fatigue dimensions during 2 years after breast cancer surgery and to explore the demographic, clinical and personality characteristics associated with these profiles. We included women from the prospective longitudinal multicenter FATSEIN cohort in France. They completed the Multidimensional Fatigue Inventory for nine follow-ups over 24 months after surgery. A group-based trajectory model identified distinct trajectories in each fatigue dimension. Multinomial logistic regression determined the factors associated with each profile. From the 459 women followed, 3-5 fatigue trajectories were revealed in each fatigue dimension, from its absence to its severest degree. In our multivariate analysis, the risk of severe fatigue was decreased in all dimensions by a high quality of life before surgery (measured by the European Organization for Research and Treatment of Cancer 30-item QoL questionnaire; e.g., for general and physical fatigue: OR = 0.93, 95% CI 0.91, 0.96), especially a high physical and emotional functions for general and physical fatigue, and a high cognitive function for mental fatigue. Both severe mental fatigue and severely reduced motivation worsened with low optimism before surgery (e.g., for mental fatigue: OR = 0.93, 95% CI 0.89, 0.97). Severely reduced activities increased by having chemotherapy (OR = 9.41, 95% CI 2.28, 38.79). Targeting women at risk for severe fatigue can provide early preventive and curative treatment and appropriate psychological support., (© 2019 UICC.)

Background: For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a real-life study., Methods: The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation., Results: The ESME research programme included 9921 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval [CI], 10.8-12.1), 5.8 (95% CI, 5.3-6.1) and 5.5 (95% CI, 4.6-6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P < 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P < 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months., Conclusions: Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: The currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme., Participants: All consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually., Finding to Date: With a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort., Future Plans: These real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings., Trial Registration Number: NCT03275311; Pre-results., Competing Interests: Competing interests: DP has received personal fees (honoraria and travel/accommodation expenses) from Laboratoire Roche, outside the submitted work. BA has received personal fees for board membership and for consultancy from Roche Pharma, outside the submitted work. SG has received personal fees for board membership from Celgene and for consultancy from Roche, outside the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An important challenge of the longitudinal analysis of health-related quality of life (HRQOL) is the potential occurrence of a Response Shift (RS) effect. While the impact of RS effect on the longitudinal analysis of HRQOL has already been studied, few studies have been conducted on its impact on the determination of the Minimal Important Difference (MID). This study aims to investigate the impact of the RS effect on the determination of the MID over time for each scale of both EORTC QLQ-C30 and QLQ-BR23 questionnaires in breast cancer patients., Methods: Patients with breast cancer completed the EORTC QLQ-C30 and the EORTC QLQ-BR23 questionnaires at baseline (time of diagnosis; T0), three months (T1) and six months after surgery (T2). Four hospitals and care centers participated in this study: cancer centers of Dijon and Nancy, the university hospitals of Reims and Strasbourg At T1 and T2, patients were asked to evaluate their HRQOL change during the last 3 months using the Jaeschke transition question. They were also asked to assess retrospectively their HRQOL level of three months ago. The occurrence of the RS effect was explored using the then-test method and its impact on the determination of the MID by using the Anchor-based method., Results: Between February 2006 and February 2008, 381 patients were included of mean age 58 years old (SD = 11). For patients who reported a deterioration of their HRQOL level at each follow-up, an increase of RS effect has been detected between T1 and T2 in 13/15 dimensions of QLQ-C30 questionnaire, and 4/7 dimensions of QLQ-BR23 questionnaire. In contrast, a decrease of the RS effect was observed in 8/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire in case of improvement. At T2, the MID became ≥ 5 points when taking into account the RS effect in 10/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire., Conclusions: This study highlights that the RS effect increases over time in case of deterioration and decreases in case of improvement. Moreover, taking the RS into account produces a reliable and significant MID.

The objective of this work was to detail the incidence and mortality trends of invasive and in situ breast cancer (BC) in France, especially regarding the development of screening, over the 1990-2008 period. Data issued from nine population-based cancer registries were studied. The incidence of invasive BC increased annually by 0.8 % from 1990 to 1996 and more markedly by 3.2 % from 1996 to 2003, and then sharply decreased until 2006 (-2.3 % per year), especially among women aged 50-69 years (-4.9 % per year). This trend was similar whatever the introduction date of the organized screening (OS) program in the different areas. The incidence of ductal carcinoma in situ steadily increased between 1990 and 2005, particularly among women aged 50-69 years and 70 and older. At the same time, the mortality from BC decreased annually by 1.1 % over the entire study period. This decrease was more pronounced in women aged 40-49 and 50-69 and, during the 1990-1999 period, in the areas where OS began in 1989-1991. The similarity in the incidence trends for all periods of implementation of OS in the different areas was striking. This suggests that OS alone does not explain the changes observed in incidence rate. Our study highlights the importance of closely monitoring the changes in incidence and mortality indicators, and of better understanding the factors causing variation.

Background: This prospective multicenter study aimed to study the impact of the recalibration component of response-shift (RS) on time to deterioration (TTD) in health related quality of life (QoL) scores in breast cancer (BC) patients and the influence of baseline QoL expectations on TTD., Methods: The EORTC-QLQ-C30 and BR-23 questionnaires were used to assess the QoL in a prospective multicenter study at inclusion (T0), at the end of the first hospitalization (T1) and, three (T2) and 6 months after the first hospitalization (T3). Recalibration was investigated by the then-test method. QoL expectancy was assessed at diagnosis. Deterioration was defined as a 5-point decrease in QoL scores, considered a minimal clinically important difference (MCID). TTD was estimated using the Kaplan-Meier method. Cox regression analyses were used to identify factors influencing TTD., Results: From February 2006 to February 2008, 381 women were included. Recalibration of breast cancer patients' internal standards in the assessment of their QoL had an impact on TTD. Median TTD were significantly shorter when recalibration was not taken into account than when recalibration was taken into account for global health, role-functioning, social-functioning, body-image and side effects of systemic therapy. Cox multivariate analyses showed that for body image, when recalibration was taken into account, radiotherapy was associated with a shorter TTD (HR: 0.60[0.38-0.94], whereas, no significant impact of surgery type on TTD was observed. For global health, cognitive and social functioning dimensions, patients expecting a deterioration in their QoL at baseline had a significantly shorter TTD., Conclusions: Our results showed that RS and baseline QoL expectations were associated with time to deterioration in breast cancer patients.

Background: The occurrence of response shift (RS) in longitudinal health-related quality of life (HRQoL) studies, reflecting patient adaptation to disease, has already been demonstrated. Several methods have been developed to detect the three different types of response shift (RS), i.e. recalibration RS, 2) reprioritization RS, and 3) reconceptualization RS. We investigated two complementary methods that characterize the occurrence of RS: factor analysis, comprising Principal Component Analysis (PCA) and Multiple Correspondence Analysis (MCA), and a method of Item Response Theory (IRT)., Methods: Breast cancer patients (n = 381) completed the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires at baseline, immediately following surgery, and three and six months after surgery, according to the "then-test/post-test" design. Recalibration was explored using MCA and a model of IRT, called the Linear Logistic Model with Relaxed Assumptions (LLRA) using the then-test method. Principal Component Analysis (PCA) was used to explore reconceptualization and reprioritization., Results: MCA highlighted the main profiles of recalibration: patients with high HRQoL level report a slightly worse HRQoL level retrospectively and vice versa. The LLRA model indicated a downward or upward recalibration for each dimension. At six months, the recalibration effect was statistically significant for 11/22 dimensions of the QLQ-C30 and BR23 according to the LLRA model (p ≤ 0.001). Regarding the QLQ-C30, PCA indicated a reprioritization of symptom scales and reconceptualization via an increased correlation between functional scales., Conclusions: Our findings demonstrate the usefulness of these analyses in characterizing the occurrence of RS. MCA and IRT model had convergent results with then-test method to characterize recalibration component of RS. PCA is an indirect method in investigating the reprioritization and reconceptualization components of RS.

Waiting times are key indicators of a health's system performance, but are not routinely available in France. We studied waiting times for diagnosis and treatment according to patients' characteristics, tumours' characteristics and medical management options in a sample of 1494 breast cancers recorded in population-based registries. The median waiting time from the first imaging detection to the treatment initiation was 34 days. Older age, co-morbidity, smaller size of tumour, detection by organised screening, biopsy, increasing number of specimens removed, multidisciplinary consulting meetings and surgery as initial treatment were related to increased waiting times in multivariate models. Many of these factors were related to good practices guidelines. However, the strong influence of organised screening programme and the disparity of waiting times according to geographical areas were of concern. Better scheduling of diagnostic tests and treatment propositions should improve waiting times in the management of breast cancer in France., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries., Methods: Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers., Results: Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER-PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER-PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%)., Conclusions: Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15-99 years during 1996-98 in 7 US states and 12 European countries. Age-standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70-99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment., (Copyright © 2012 UICC.)

Purpose: To characterize response shift effects in patients with breast cancer (BC)., Methods: The QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and at the end of the first hospitalization. We used the then-test approach to characterize changes in internal standards by calculating the mean difference between the then-test (retrospective measure) and pre-test baseline QoL assessments. The Ideal Scale Approach was also used to assess changes in standards by comparing health and QoL expectancies between baseline and the end of the first hospitalization. Successive Comparison Approach was used to assess changes in values through the longitudinal assessment of the relative importance of EuroQOL dimensions., Results: The results of this study showed that recalibration RS effects occurred early after the first hospitalization for 6/15 dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss, diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects). Moreover, health and QoL expectancies changed between the baseline and the end of the first hospitalization, and changes in values were seen for the self-care and usual activities dimensions of the EuroQOL-EQ-5D., Conclusions: The occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC.

Purpose: Fatigue is one of the most frequent symptoms in patients with cancer. However, the precise determinants of fatigue are still unknown. This study was conducted to investigate factors correlated with cancer-related fatigue before surgery and just before subsequent adjuvant therapy., Methods: Patients completed the Multidimensional Fatigue Inventory (MFI-20), the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire before and after surgery, the Trait Anxiety Inventory and the Life Orientation Test before surgery, and the State Anxiety Inventory before the start of adjuvant therapy. Multiple regression analysis of determinants of change in MFI-20 total score after surgery was conducted., Results: A series of 466 eligible patients with stage I-III breast cancer with planned surgery were recruited. An increase in MFI-20 total score after surgery was significantly correlated with higher preoperative fatigue and lower role functioning before surgery; a decrease in role functioning, physical functioning, and cognitive functioning after surgery; an increase in insomnia after surgery; and a higher state anxiety after surgery. Disease stage, lymph node metastases, surgical procedure, and demographic characteristics (e.g., age, marital status, having children, educational level) were not correlated with fatigue in multivariate analysis., Conclusion: These results suggest that worsening fatigue after surgery for breast cancer is associated with a decrease in physical functioning and an increase in psychological distress rather than with the cancer characteristics. Therefore, screening measures should be implemented at the time of diagnosis-before starting treatment-to identify psychologically vulnerable patients and to offer them professional support.

Background: Secondary tumours (ST) represent a major concern in survivors of Hodgkin's disease (HD). Breast cancer (BC) is the most frequent ST among young treated women., Material and Methods: One hundred and eighty-nine women treated for HD by radiotherapy (RT) and/or chemotherapy (CT) subsequently developed 214 BCs., Results: Median age at HD diagnosis was 25 years (34% were less than 20). Median interval between HD and BC was 18.6 years, with a 42-year median age at first BC. According to the TNM classification, there were 30 (14%) T0 (non palbable lesions), 86 (40%) T1, 56 (26%) T2, 13 (6%) T3T4 and 29 (14%) Tx. There were 25 (13.2%) contralateral BC. 160 (75%) and 15 (7%) tumours were infiltrating ductal and lobular carcinomas, 7 (3.3%) were other subtypes and 27 (22%) DCIS. The rate of axillary nodal involvement was 32%. Among 203 operated tumours, 79 (39%) were treated by breast conserving surgery (BCS), with RT in 56 (71%) cases. CT and hormonal treatment were delivered in 51% and 45% of the patients. With a 50-month median follow-up, local recurrence occurred in 12% of the tumours (9% after mastectomy, 21% after lumpectomy alone and 13.7% after lumpectomy with RT). Metastasis occurred in 47 (26%) patients. The risk factors were pN+, pT, high SBR grade and young age (< 50 years). The ten-year overall and specific survival rates were 53% and 63.5%, respectively. The ten-year specific survival rates were 79% for pT0T1T2, 48% for pT3T4 (p = 0.0002) and 79% for pN0 versus 38.5% for pN+ (p = 0.00026). Among 67 deaths, 43 (73%) were due to BC., Conclusion: Patients and physicians should be aware that BC is the most frequent secondary tumour in young women treated for HD. The new RT modalities (lower doses and involved fields) may decrease the risk in the future. However, these women require a careful monitoring as from 8 to 10 years after HD treatment, combining mammography, ultrasound and MRI according to several ongoing studies. BC with whole breast irradiation is feasible in some selected cases., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Population-based studies on quality of life (QOL) of long-term breast cancer survivors are quite recent and insufficient attention has been paid to the effect of time since diagnosis. We compared long-term QOL of population-based breast cancer survivors 5, 10, and 15 years after diagnosis with that of healthy controls. Breast cancer survivors were randomly selected from three population-based cancer registries (Bas-Rhin, Calvados and Doubs, France) along with healthy controls, stratified for age and place of residence, randomly selected from electoral rolls. Participants completed five self-administered questionnaires: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Short Form-36 (SF-36), Spielberger State-Trait Anxiety Inventory (STAI), Multidimensional Fatigue Inventory (MFI) and a life conditions questionnaire. An analysis of variance was used to compare QOL scores of breast cancer survivors by period (5, 10, or 15 years) of diagnosis with those of controls, adjusted for sociodemographic data and comorbidities. Six hundred and fifty-two cases and 1,188 controls participated in the study. For many QOL scales, scores were significantly different between cancer survivors and controls. A clinically significant difference was evidenced for the fatigue scales, the SF36 physical functioning, role-physical, and role-emotional scales, with more favorable results for controls. Differences decreased with time and 15-year cancer survivors were generally not different from controls. Scores were particularly influenced by age and mean household income. More efforts should be made, specifically during the first 5 to 10 years after diagnosis, to help women with breast cancer to overcome their impairment in QOL.

Absence of hormonal receptors (HR) expression is a predictive factor of high pathologic complete response (pCR) rate after neo-adjuvant chemotherapy. However, HR-positive tumors are less chemosensitive. In the present study, we evaluated the predictive value of estrogen (ER) and progesterone (PgR) semi-quantitative expression in patients with HR-positive tumors treated uniformly with antracycline-based neoadjuvant chemotherapy without hormonal treatment. Value of HR expression as a predictive factor was then evaluated in a multivariate analysis with tumor grade, Ki67 index and HER2 expression. From January 2000 and December 2006, 177 patients with HR-positive breast ductal invasive carcinoma ≥2 cm in its largest diameter were treated with six cycles of an anthracycline-based neo-adjuvant chemotherapy. Tumor grade, ER, PgR, HER2 status and Ki67 index were determined on microbiopsy performed before chemotherapy. A semi-quantitative evaluation of ER and PgR expression by IHC was performed using the Barnes'score. pCR rate was significantly different (P < 0.001) according to the ER expression score. pCR rate was 28% for low score, 9% for medium score and 3% for high score. On the contrary, pCR rate was not significantly different (P = 0.49) according to the PgR expression score. In the multivariate analysis, ER expression score (P = 0.0002) and Ki67 index (P = 0.02) were the only predictive factors of response for HR-positive tumors. pCR after anthracycline-based chemotherapy is significantly correlated with the ER expression score.

Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and only for cancers T2 and/or N+ (whether 1, 2 or 3) and M0, the prognosis was significantly better when the diagnosis mammography was done within the framework of screening. Socio-economic and surveillance characteristics are independent prognostic factors of both breast cancer stage at diagnosis and of survival. Screening mammography is an independent prognostic factor of survival.

The aim of this study was to evaluate the predictive value of five different biological factors in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston-Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR). 119 patients with operable breast cancer were treated with six cycles of FEC (100 5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2). Tumour response was assessed clinically and by computed tomography (CT) scan, then by pathological assessment. The clinical overall response (OR) was 80%, with 19% of complete responders (CR). The radiological OR was 71%, with 16% of CR. A pathological CR was demonstrated in 13% of the patients according to the Sataloff classification. In the multivariate analysis, the absence of HR expression and Ki-67 > or = 20% were predictive for a clinical CR. A high tumour grade was predictive for a pathological CR. Overexpression or amplification of HER2 or Topollcalpha were not predictive of response.

Background: Axillary lymph node involvement (ALNI) remains the most accurate predictive factor for recurrence risk and survival in patients with invasive breast carcinoma (IBC) and is an essential element in therapeutic decisions. However, axillary dissection (AD) is responsible for several side effects and is now discussed in small IBC. The objective of this study was to define a predictive model of ALNI by using clinical and histologic variables available before surgery., Methods: The authors studied 795 cases of IBC (T0, T1, T2 < or = 4 cm; N0; M0) treated between 1980 and 1997 by conservative surgery and radiation therapy. All cases had axillary dissection with at least 10 lymph nodes removed. A stepwise logistic regression analysis was performed to build a predictive model of ALNI. The authors then used the jackknife resampling technique to produce unbiased estimates of the probabilities of ALNI along with their confidence intervals., Results: The global ALNI rate was 25.7%. The final predictive model included clinical tumor size, location, and histologic subtype and grade as variables independently associated with ALNI. The estimated probability of ALNI varied from 6% to 45%, according to case characteristics for these variables., Conclusions: These results show that the omission of AD in surgical procedures for these tumors is debatable. Even when ALNI rates were low, the superior bounds of the confidence intervals could be high. Consequently, we do not recommend to omit AD in women whose estimated risks are higher than 25%. Women with a risk of ALNI lower than 25% could benefit from the sentinel lymph node procedure with, likewise, a limited risk of false-negative.

Purpose: To analyze the main determinants of lymph nodal recurrence in early breast cancer and to compare our results with literature data., Methods: Retrospective analysis of 1119 patients with stage I-II infiltrating breast cancer treated by conservative radiosurgical association from 1980 to 1992, with a 10-year median follow-up., Results: The global rate of lymph nodal recurrence (LNR) was 2.7% (30 cases). Age under 40, high histoprognostic grade and previous local recurrence were the main risk factors of LNR. Axillary nodal involvement at time of diagnosis, number of lymph nodes sampled and tumor localization were not significantly related to LNR., Conclusion: Lymph nodal recurrences of early breast cancers are not frequent, but their prognosis is very unfavourable. A multidisciplinary approach of these LNR is necessary, taking into account previous treatments.

Purpose: To assess the clinical and histological characteristics of breast cancer (BC) occurring after Hodgkin's disease (HD) and give possible therapies and prevention methods., Materials and Methods: In a retrospective multicentric analysis, 117 women and two men treated for HD subsequently developed 133 BCs. The median age at diagnosis of HD was 24 years. The HD stages were stage I in 25 cases (21%), stage II in 70 cases (59%), stage III in 13 cases (11%), stage IV in six cases (5%) and not specified in five cases (4%). Radiotherapy (RT) was used alone in 74 patients (63%) and combined modalities with chemotherapy (CT) was used in 43 patients (37%)., Results: BC occurred after a median interval of 16 years. TNM classification (UICC, 1978) showed 15 T0 (11.3%), 44 T1 (33.1%), 36 T2 (27.1%), nine T3 (6.7%), 15 T4 (11.3%) and 14 Tx (10.5%). Ductal infiltrating carcinoma and ductal carcinoma in situ (DCIS) represented 81.2 and 11.3% of the cases, respectively. Among the infiltrating carcinoma, the axillary involvement rate was 50%. Seventy-four tumours were treated by mastectomy without (67) or with (ten) RT. Forty-four tumours had lumpectomy without (12) or with (32) RT. Another four received RT alone, and one CT alone. Sixteen patients (12%) developed isolated local recurrence. Thirty-nine patients (31.7%) developed metastases and 34 died; 38 are in complete remission whereas five died of intercurrent disease. The 5-year disease-specific survival rate was 65.1%. The 5-year disease-specific survival rates for the pN0, pN1-3 and pN>3 groups were 91, 66 and 15%, respectively (P<0.0001), and 100, 88, and 64% for the TIS, T1 and T2. For the T3 and T4, the survival rates decreased sharply to 32 and 23%, respectively. These secondary BC are of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN>3 and/or T3T4), and many tumours with a 'slow spreading' such as DCIS and microinvasive lesions. These lesions developed especially in patients treated exclusively by RT., Conclusions: The young women and girls treated for HD should be carefully monitored in the long-term by clinical examination, mammography and ultrasonography. We suggest that a baseline mammography is performed 5-8 years after supradiaphragmatic irradiation (complete mantle or involved field) in patients who were treated before 30 years of age. Subsequent mammographies should be performed every 2 years or each year, depending on the characteristics of the breast tissue (e.g. density) and especially in the case of an association with other BC risk factors. This screening seems of importance due to excellent prognosis in our T(1S)T(1) groups, and the possibility of offering these young women a conservative treatment.

Axillary nodal involvement (ANI) remains an essential prognostic factor for breast cancer patients, as it implies the necessity of systemic adjuvant treatment and locoregional irradiation. Axillary dissection (AD) contributes to improved local disease control and may increase survival. However, AD results in a 10%-25% incidence of long-term side effects, particularly lymphedema. Moreover, many small primary lesions with low risk of ANI are now discovered by screening, and it is not clear whether AD should be used routinely in all such patients. Sentinel lymph node biopsy (SLNB) is a selective procedure that allows selective staging of the axilla with few side effects. However, indications for SLNB are not precisely defined yet, so some patients may be understaged and the axillary relapse rate may increase. This study was conducted to help clinicians assess the risk of ANI and analyzed six clinical and histological parameters to optimally recognize patients who might benefit from SLNB, with a minimal risk of false-negative rate. We retrospectively analyzed the ANI risk among 893 women treated by conservative surgery and radiation for T0, T1, or T2 invasive tumours < 3 cm in size. All patients underwent AD with sampling of a minimum of seven lymph nodes. In each case, we assessed the clinical and pathological tumor size, histological subtype (including grading), tumor location, age at diagnosis, and breast size. The global ANI rate in the entire cohort was 25.3%. In multivariate analysis, three variables were significantly predictive of the ANI risk: tumor size (P < 0.0001), histological subtype (P = 0.0005), and breast size (P = 0.004). By combining these parameters, we were able to define three categories of women with low (< 20%), intermediate (21%-25%), and high (> 25%) ANI risk. We suggest that women with nonpalpable (T0), T1 grade 1/2, and T2 < 3 cm tumors of medullary, mucinous, tubular, or papillary histological subtype are the best candidates for SLNB. For other patients with a higher ANI risk tumor, AD may still remain the best procedure to obtain accurate staging and definitive local control.

The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for invasive breast cancer and the predictability of axillary node status. Between January 1996 and June 1997 a total of 73 patients underwent patent blue dye lymphatic mapping and sentinel node biopsy followed by standard (level I and II) axillary node dissection (one bilateral procedure). The sentinel node was identified in 82.4% (61/74) of the cases and was predictive of axillary status in 96.7% (59/61). The false-negative rate of the procedure was 8.0% (2/25). The sentinel node was involved in 37.7% (23/61) and was the only one invaded in 30.4% (7/23). The sensitivity of the procedure was 92% (CI95% 74-99%) and its specificity 100%. It is currently considered to be an attractive new procedure undergoing evaluation in prospective controlled trials. This study confirmed the reliability and reproducibility of intraoperative lymphatic mapping and sentinel node biopsy. This is the first step toward a new era of minimally invasive axillary surgery for breast cancer.

Aim of the Study: The goal of this study was to evaluate the technical feasibility of sentinel node biopsy in breast cancer and its predictivity of axillary node status., Patients and Methods: Between January 1996 and June 1997, 128 patients with invasive breast carcinomas, referred to the Cancer Center of Strasbourg and Lyon (France), underwent lymphatic mapping (Patent Blue dye) and sentinel node biopsy followed by axillary clearance (Berg's level I to II)., Results: Sentinel node was identified in 76.5% of cases and was predictive of axillary status in 94.9% of cases. The false negative rate of the procedure was 5.1%. Sentinel lymph node was involved in 43.9% of cases and it was the only one involved in 30.2% of cases. The sensitivity of the procedure was 94% (CI: 95% = [88%-98%]) and its specificity 100%., Conclusion: Actually considered as new attractive procedure under ongoing evaluation in prospective controlled trials, this study confirms the feasibility and reproductibility of lymphatic mapping and sentinel node biopsy, first stage before entering a new era of minimally invasive axillary surgery in breast cancer.

Study Aim: The aim of the study was to assess, by clinical and histological predictive factors, the axillary lymph-node involvement (pN+) in early breast cancers., Materials and Methods: Eight hundred ninety-three patients with unilateral invasive breast cancer were studied. The evaluated parameters included clinical size (T), pathological size (pT), histological subtype (ductal infiltrating, according to grading 1, 2, 3, lobular infiltrating and others), age (less than 40, 40 to 60 and above 60). Furthermore, a new parameter, the dosimetric breast size, recently described, was included (Eur J Cancer 1997; 33: 2432-4)., Results: The global rate of pN+ was 25.3%, with respectively, pN1: 10%, pN2-3: 8.4% and pN > 3: 6.9%. According to T, the pN+ rates were, respectively, 13.8%, 19.8% and 36.2% in the T0, T1 and T2 < or = 3 cm groups. According to pT, the pN+ rates were, respectively, 11.1%, 17.7%, 23.5%, 30.1% and 36% in the following groups: 0-9.9 mm, 10-14.9 mm, 15-19.9 mm, 20-24.9 mm and 25-29.9 mm. For the ductal infiltrating carcinoma, according to the gradings 1, 2 and 3, we found, respectively, 18.3%, 27.2% and 37.8% of pN+. For the lobular infiltrating carcinoma and the other histological subtypes, the rates were 22.7% and 10%, respectively. For the three age categories cited above the pN+ rates were, respectively, 30.3%, 25.8% and 22.4%. According to breast size we found 30.1% and 24.4% of pN+ respectively for small and medium or large dosimetric breast size. After a multivariate analysis, three factors were significant for pN+ risk: clinical tumor size (P = 0.0001), histological subtype (P = 0.0005) and dosimetric breast size (P = 0.004). With a combination of these three factors, the pN+ rates varied from 5% to 50%., Conclusions: The authors conclude that both clinical and pathological characteristics of the primary tumor (specified by previous core biopsy) can indicate the risk for axillary node metastases, and allow selection of candidates for limited axilla surgery (sentinel node).

In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pN > or = 3 groups were 91%, 66% and 0%, respectively (P < 0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN > 3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.

To evaluate the risk of local recurrence following breast-conserving therapy for breast cancer, we measured the distance between each entry point of the irradiation on the surface of the breast in line with the axis of the external and internal tangential fields (dosimetric breast size). 652 breast cancer patients were retrospectively analysed, with a median age of 51 years and a median follow-up of 99 months (range 84-192). There were 50 local recurrences, 44 isolated and 6 associated with nodal recurrence or metastases. The global rates of local recurrences at 5 and 10 years were 5.3% and 9%, respectively (Kaplan-Meier analysis). Following a Cox's multivariate analysis, the only significant and independent parameters related to local recurrence were quality of excision, age at diagnosis and dosimetric breast size. For a small dosimetric breast size (< or = 10 cm), the rate of local recurrence was 14.1 compared with 11.8 for medium dosimetric breast size (> 10 cm-< or = 12 cm) and 5.2 for large dosimetric breast size (> 12 cm). If the analysis was restricted to only those with complete excision, then the relative risk for a patient with a small dosimetric breast size was three times that for a large breast size.

Tamoxifen is the anti-estrogen the most widely used in breast cancer. The duration of its prescription, as adjuvant treatment, tends to increase (5 years, and even more) and now it is used in chemoprevention. A slight increase of thromboembolic complications was noted in some studies. This article evaluates the frequency of thromboembolic accidents (TEA) in 441 postmenopausal patients treated by an association of conservative radiosurgery, tamoxifen +/- chemotherapy, for a breast carcinoma T0, T1T2 < 4 cm. Nineteen patients (4.3%), all in remission, presented a TEA, between 1 and 44 months after the beginning of the tamoxifen treatment. We observed seven pulmonary embolisms (PE), 11 deep venous thromboses (DVT) and an acute arterial ischemia. Two patients aged 74 and 80 years died, the others had a favourable evolution under anticoagulant treatment. Among these 19 patients, six presented known risks factors (phlebitis, cardiovascular disorders) and ten had a "favouring circumstance" aggravating the risk of TEA (surgical operation, severe infection, fracture). Their median age was 65 years (61 for all the 441 patients). We noted eight cases of breast lobular cancer (42%) among these 19 patients (11% for all the patients). Among postmenopausal patients, the indication of tamoxifen must be evaluated according to the benefits expected in those with high risk factors of TEA (history of heart failure, obesity, spread varix, age > 65 years). In case of DVT and/or PE, this treatment seems contra-indicated. In case of "favouring circumstances", a hypocoagulant or systematic anticoagulant treatment must be proposed. In case of combined chemotherapy, it is better to start tamoxifen at the end of the treatment. These simple prophylactic measures should allow to reduce significantly the risk of TEA in postmenopausal patients with adjuvant anti-estrogenotherapy.

Objectives: With effective screening programmes, the global incidence of in situ ductal carcinoma of the breast has risen to 15%, representing 20 to 30% of the mammographically detected T0 tumours. Prognosis is generally good in these tumours, but treatment has in the past, paradoxically, relied on extensive surgery. We report our experience with conservative radiosurgery performed in such cases from 1980 to 1990., Methods: There were 86 patients with a mean age of 52 years. Initial TNM classification was T0 = 57, T1 = 17, T2 = 9 and Tx = 3. All underwent limited surgery (quadrantectomy: 17; lumpectomy: 69) and 49 had axillary dissection. All received breast irradiation with scar boost (46-50 Gy + 10-14 Gy with classical fractionation). Thirty one postmenopausal women received adjuvant tamoxifen. The quality of the resection was good in 77 cases, doubtful or incomplete in 9. In one case axillary nodal involvement was found. The histological subtype was clearly identified in 63 cases. With a median follow-up of 58 months, 3 local relapses occurred (3.4%), at 27, 48 and 52 months respectively. One was in situ and two invasive. All were clinical lesions (2 T1 and 1 T2); two had incomplete or doubtful excision and all received less than 60 Gy on the tumour bed. All had mastectomy. Two are alive and well but one developed multiple metastasis. Five other women had subsequent surgery for suspicion of local relapse but all had benign disease. One developed contralateral disease 20 months later. Two women died subsequently due to a second cancer., Conclusion: These results confirm the importance of the excision quality and suggests a possible dose-effect in the control of in situ ductal carcinoma by radiotherapy. The recent results of the B-17 NSBAP trial also conclude that the radiosurgical conservative treatment, for limited in situ ductal carcinoma, is a reasonable alternative to mastectomy.

Gradual tumor tissue devascularization during mastectomy is thought to decrease estrogen (ER) and progesterone (PgR) receptor activity. To determine whether or not hormone receptor values could be influenced by different mastectomy techniques, 62 patients with carcinoma of the breast had a Tru-cut needle (Baxter Healthcare Corporation) biopsy (premastectomy sample) and underwent modified radical mastectomy (postmastectomy sample) either before (group 1, 40 patients) or after (group 2, 22 patients) axillary lymph node dissection. When the two surgical procedures were compared in 33 patients in whom it could be assessed, no significant tendency (p = 0.51 for ER and p = 0.36 for PgR) for the postmastectomy sample to have hormone receptors levels less than samples taken at biopsy was detected. Overall, in the two groups (44 assessable patients), comparison with respect of each patient, between premastectomy and postmastectomy samples showed that the variations in either ER or PgR receptor values, determined by immunoenzymatic assays, were not statistically significant (p = 0.32 for ER and p = 0.21 for PgR). The current results indicated the relative stability of steroid receptors during the two modified radical mastectomy procedures and suggested that a systematic reference determination of hormone receptors on biopsy before modified radical mastectomy is unnecessary.

In a retrospective and multicentre study 106 cases treated from 1970 to 1985 were analysed. The patients' median age was 64 years. TNM classification showed 20 T1, 48 T2, 2 T3, 32 T4 and 4 Tx. Twenty one patients had clinical gynaecomastia; 99 underwent surgery and 85 radiotherapy; 32 received adjuvant chemotherapy or hormonal therapy. The main histological type was ductal infiltrating carcinoma; 82 axillary dissections were performed, and positive lymph nodes were found in 67 percent of the cases. Hormone receptors were positive in 15 out of 20 measured cases. Five and 10 years overall survival rates (Kaplan-Meier) were 57 and 37 percent, and corrected survival rates 68 and 55 percent respectively. The main prognostic factor remains the clinical size of the tumour (T) and histologically axillary node status (pN). Eleven patients developed a second metachronous cancer. The aetiology of male breast cancer is a poorly known as that of female breast cancer. Nevertheless, imbalance among oestrogens and androgens due to metabolic, infectious or pharmacological causes is probably responsible, at least in part, for this cancer. An on-going multicentre prospective national trial tries to address this question.

Male breast cancer represents about only 1% of all breast cancers. We have analysed a retrospective, multicentric series of 404 patients, initially non-metastatic, with mean age of 63 years. The 5 and 10-year overall survival rates were 65 and 36% respectively. Sixty-eight patients developed secondary cancer. From ten patients who already presented with cancer (2.5%) 3 cases corresponded to prostatic cancer treated by estrogen. Four had synchronous cancer (1%). Three and eight patients respectively had a synchronous and metachronous contralateral breast cancer (2.7% of bilateral cancer). Forty-three other patients (10.6%) developed metachronous cancer. The main tumor types were: prostate (9), lung (6), colon and rectum (6), esophagus (4). Four patients developed various hematologic malignancies and 14 patients, various types of solid tumors. From these 43 patients, 27 died; 19 as a result of secondary cancer. This represents 9% of all deaths among the 404 patients. While the bilateral cancer rate is similar to women, the second cancer rate appears to be higher in men. From hematological malignancies, chemotherapy and radiotherapy do not seem to contribute to this high incidence of second cancer.