Isolated ipsilateral local recurrence of breast cancer: predictive factors and prognostic impact.

BACKGROUND: Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points. METHODS: Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes. RESULTS: Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p < 0.0001), endocrine therapy (HR 2.05, p < 0.0001) and age < 40-years old (HR 2.28, p = 0.005) in MVA. When MVA was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR 4.96 for ILR-free interval between 2 and 5-years and HR 9.00 when < 2-years, in comparison with ≥ 5-years). CONCLUSION: ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.

Adjuvant chemotherapy in lobular carcinoma of the breast: a clinicopathological score identifies high-risk patient with survival benefit.

BACKGROUND: Invasive lobular carcinomas (ILCs) represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) is still unclear. METHODS: Our objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,319 patients who underwent primary surgery in 15 French centers between 1990 and 2014. Only ILC, hormone-positive, human epidermal growth factor 2 (HER2)-negative patients who received adjuvant endocrine therapy (ET) were included. End-points were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT, aiming to compensate for baseline characteristics, was used. RESULTS: Of a total of 2318 patients with ILC, 1485 patients (64%) received ET alone and 823 (36%) received ET + CT. We observed a beneficial effect of addition of CT to ET on DFS and OS in multivariate Cox model (HR = 0.61, 95% confidence interval, CI [0.41-0.90]; p = 0.01 and 0.52, 95% CI [0.31-0.87]; p = 0.01, respectively). This effect was even more pronounced when propensity score matching was used. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT. CONCLUSION: ILC patients could derive significant DFS and OS benefits from CT, especially for high-risk patients.

[Update of indications and techniques for the management of lymphedema after breast cancer surgery]. / Actualisation des indications et des techniques de prise en charge du lymphœdème après chirurgie du cancer du sein.

OBJECTIVES: Upper limb lymphedema secondary to breast cancer treatment is the leading cause of lymphedema in France. Despite improved surgical practices and de-escalation of radiotherapy, the risk of lymphedema after breast cancer still affects 5-20% of patients, with this variation depending on the measurement method used and the population studied. Lymphedema has a negative impact on quality of life and body image, and their possible occurrence remains a major concern for all women treated for breast cancer. The Sénologie Commission of the Collège national des gynécologues et obstétriciens français (CNGOF) asked four specialists in breast surgery or lymphology to prepare a summary on the prevention, medical and surgical management of lymphedema after breast cancer treatment, and to discuss the medical and surgical innovations currently being evaluated. METHODS: This synthesis was based on national and international guidelines on the management of upper limb lymphedema after breast surgery and a recent review of the literature focusing on the years 2020-2023. RESULTS: From a preventive point of view, the restrictive instructions imposed for a long time (reduction in physical activity or the carrying of loads, air travel, exposure to the sun or cold, etc.) have altered patients' quality of life and should no longer be recommended. A good understanding of risk factors enables us to target preventive actions. Examples include obesity, a sedentary lifestyle, axillary clearance, radiotherapy of the axillary fossa in addition to axillary clearance, total mastectomy, taxanes or anti-HER-2 therapies in the adjuvant phase. Resumption of physical activity, minimally invasive axillary surgery, de-escalation of radiotherapy and breast-conserving surgical procedures have all demonstrated their preventive value. When lymphedema does occur, early management, through complete decongestive physiotherapy, can help reduce its volume and prevent its long-term worsening. CONCLUSION: Surgical (lymph node transplants, lympho-vascular anastomoses) and medical (prolymphangiogenic growth factors) approaches to lymphedema treatment are numerous, but require long-term evaluation of their efficacy and adverse effects.

French college of gynecologists and obstetricians (CNGOF) recommendations for clinical practice: Place of breast self-examination in screening strategies.

Breast cancer is the most common female cancer in the world. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of formal breast self-examination (BSE) as opposed to breast awareness has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: The Commission of Senology (CS) of the Collège National de Gynécologie et Obstétrique Français (CNGOF) respected and followed the Grading of Recommendations Assessment, Development and Evaluation method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE versus abstention from this examination led to detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from clinical breast examination by practitioners from the age of 25, and from organized screening from 50 to 74 (strong recommendation). In the absence of data on the benefits of BSE in patients aged over 75, for those at high risk and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these categories wish to undergo BSE, information on the benefits and risks observed in the general population must be given, notably that BSE is associated with a higher number of referrals, biopsies, and a reduced quality of life.

Information and oncosexological management in breast cancer patients.

OBJECTIVES: Breast cancer treatment is a particularly high-risk situation for the deterioration of sexual health, leading to an alteration in body image and physical deteriorations such as vaginal trophicity. The aim of this study was to evaluate the information received by patients concerning this alteration of their sexual health in relation to their treatment, and to identify their expectations and needs in terms of oncosexual management. STUDY DESIGN: A bicentric qualitative retrospective study was conducted, involving women aged 18 to 80, treated for breast cancer by total or partial mastectomy after 2014 and having had a follow-up consultation between July and December 2019. Data were collected using medical files and a de-identified questionnaire sent by post or e-mail after obtaining consent. The main outcome measures were the proportion of patients who received informations about oncosexology and those who felt impact on their sexual health. RESULTS: Of the 274 patients included in the study, 60% said they had received no information about the sexological side effects of their disease or treatment. Of these, 62.5% dared not talk about it during consultation. Patients were keen to receive oncosexological advice or treatment from a specialized nurse or doctor. In 76.1% of cases, patients declared that they had been sexually active in the year prior to their cancer diagnosis, compared with 54.94% after treatment. They reported a loss of femininity in 24% of cases, and 40.5% had no sexual desire. CONCLUSION: Women treated for breast cancer report a lasting alteration in their body image and sexual activity. Information on the impact of the disease and its treatment on sexual health is inadequate, even though patients are keen to receive specialized care with professional sexology consultations. The impact of breast cancer on sexual health should systematically explained to the patients, especially as treatment options exist and can be offered.

Negative Survival Impact of Occult Lymph Node Involvement in Small HER2-Positive Early Breast Cancer Treated by Up-Front Surgery.

(1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5-64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04-5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03-6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients.

Early breast cancer in women aged 35 years or younger: A large national multicenter French population-based case control-matched analysis.

BACKGROUND: There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a control group aged 36 to 50. METHODS: Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36-50 years patients. RESULTS: Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS [HR 1.56, 95% CI 1.32-1.84; p < 0.001], and OS [HR 1.29, 95% CI 1.03-1.60; p = 0.025], as were high grade, large tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS [HR 1.56, 95%CI 1.28-1.91, p < 0.001], and OS [HR 1.33, 95%CI 1.02-1.73, p = 0.032]. When only considering patients ≤35, ER, tumor size, nodal status, and LVI were independently associated with survival in this subgroup. CONCLUSIONS: Age ≤35 is associated with less favorable presentation and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments.

[Place of breast self-examination in screening strategies. French College of Gynecologists and Obstetricians (CNGOF) recommendations for clinical practice]. / Recommandations pour la pratique clinique du CNGOF. Place de l'auto-examen des seins dans les stratégies de dépistage.

OBJECTIVES: Breast cancer is the most common female cancer in the world. In France, over 60,000 new cases are currently diagnosed, and 12,000 deaths are attributed to it annually. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of breast self-examination (BSE) has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: the CNGOF's Commission de Sénologie (CS), composed by 17 experts and 3 invited members, drew up these recommendations. No funding was provided for the development of these recommendations. The CS respected and followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions concerning BSE, individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE compared with abstention from this examination led to the detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from a clinical breast examination (by the attending physician or gynecologist) from the age of 25, and from organized screening from 50 to 74 (strong recommendation). However, in the absence of data on the role of BSE in patients aged over 75, those at high risk of breast cancer and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these latter categories wish to undergo BSE, they must be given rigorous training in the technique, and information on the benefits and risks observed in the general population. Finally, the CS invites all women who detect a change or abnormality in their breasts to consult a healthcare professional without delay. CONCLUSION: BSE is not recommended for women in the general population. No recommendation can be established for women aged over 75, those at high risk of breast cancer and those previously treated for breast cancer.

The need to tailor the omission of axillary lymph node dissection to patients with good prognosis and sentinel node micro-metastases.

BACKGROUND: Results of IBCSG-23-01-trial which included breast cancer patients with involved sentinel nodes (SN) by isolated-tumor-cells or micro-metastases supported the non-inferiority of completion axillary-lymph-node-dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN-micro-metastases. METHODS: To investigate the impact of cALND omission on disease-free-survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients <75 years old with SN-micro-metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan-Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission. RESULTS: Weighted log-rank tests comparing adjusted Kaplan-Meier survival curves showed significant differences in OS (p-value = 0.002) and borderline significant differences in DFS (p-value = 0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR = 2.77, CI95% = 1.36-5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND. CONCLUSIONS: Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time.

Contribution of endocrine therapy in oestrogen receptor-positive pT1a-b breast cancer: Results of a retrospective study.

INTRODUCTION: Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET in such patients. METHODS: Our retrospective observational study included 5545 patients with pT1a-b ER-positive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression. RESULTS: Most patients (80.3%: 4453) received ET and-when compared to those without ET-experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR = 1.275, p = 0.047, 95% CI[1.003-1.620]) but not OS or RFS in all patients, while in 2363 patients with pT1a-b ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR = 1.502, p = 0.049, 95% CI[1.001-2.252]), but not OS (HR = 1.361, p = 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC. CONCLUSION: Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC-and especially in those with grade 2-3 tumours-no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours.

Surgical outcomes of laparoscopic hysterectomy for enlarged uteri.

STUDY OBJECTIVE: To compare surgical outcomes of laparoscopic hysterectomy for benign diseases according to the uterine weight. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: Teaching and research hospital, a tertiary center. PATIENTS: Women undergoing laparoscopic hysterectomy for benign diseases. INTERVENTIONS: Patients were divided into three groups according to the uterine weight: <250 g (n = 1300), 250 to 500 g (n = 614), and >500 g (n = 178). MEASUREMENTS AND MAIN RESULTS: Primary outcomes were differences in conversion rates, operating time, and blood loss. Secondary outcomes were differences in length of hospital stay, time to first bowel movement, time of bladder catheterization, and complications. Operating time increased according to the uterine weight (116.5 vs 124.1 vs 133 minutes; p <.001). The rate of conversion was statistically higher only for patients with uteri >500 g (3.3% vs 5% vs 13.5%; p <.001). However, the difference between preoperative and postoperative hemoglobin levels was equivalent for the three groups, as well as the overall rates of minor and major intraoperative complications. There was no difference in the time of bladder catheterization, time to first bowel movement, length of hospital stay, and incidence of minor and major postoperative complications among the three groups. CONCLUSION: Despite longer operating time, there is no increase in the intraoperative or postoperative complication rates in those patients with enlarged uteri undergoing laparoscopic hysterectomy. Only conversion is higher in patients with uteri >500 g.

Impact of the surgical peritoneal environment on pre-implanted tumors on a molecular level: a syngeneic mouse model.

BACKGROUND: We recently demonstrated that a CO(2) pneumoperitoneum at either a high or low IPP has few if any short term effects on peritoneal dissemination when tumors are well established before surgery. The objective of the present study was to evaluate the impact of the surgical peritoneal environment on pre-implanted tumors on a molecular level. MATERIALS AND METHODS: On day 7, C57BJ6 mice received an intraperitoneal inoculation of a mouse ovarian cancer cell line (ID8). On day 0, mice were randomized into four groups: anesthesia alone, CO(2) pneumoperitoneum at a low (2 mm Hg) or high (8 mm Hg) IPP, or laparotomy. Groups were further subdivided into four groups and a laparotomy was performed to collect pre-implanted tumors on POD 1, 2, 7, or 14. Expression levels of beta-1 integrin, cMet, uPA, uPAR, and PAI-1 mRNA in pre-implanted nodules were measured using real-time PCR. RESULTS: Expression levels of uPA, uPAR, and cMet mRNA were significantly higher in the laparotomy group than in the control group on POD 1. We detected significantly higher expression levels of uPAR and cMet in the laparotomy group than in the control group on PODs 2 and 7. There were no significant differences in the expression levels of any genes examined among the low IPP, anesthesia alone, and control groups on POD 1, 2, 7, or 14. CONCLUSION: The impact of a CO(2) pneumoperitoneum at a low IPP on gene expression levels of pre-implanted tumors might be minimal until POD 14 in the present mouse model.

Impact of surgical peritoneal environment on postoperative tumor growth and dissemination in a preimplanted tumor model.

BACKGROUND: We recently demonstrated that CO(2) pneumoperitoneum at low intraperitoneal pressure (IPP) had few if any short-term effects on peritoneal dissemination when an ovarian cancer cell line was inoculated just prior to surgery. The objective of the present study was to evaluate the impact of surgical peritoneal environment on postoperative tumor growth and dissemination over time when tumors were present before surgery. METHODS: On day-7, C57BJ6 mice received an intraperitoneal inoculation of a mouse ovarian cancer cell line (ID8). On day 0, mice were randomized into four groups: anesthesia alone, CO(2) pneumoperitoneum at a low (2 mmHg) or high (8 mmHg) IPP, or laparotomy. Groups were further subdivided into four groups of eight animals each and a laparotomy was performed to evaluate dissemination on postoperative day (POD) 1, 2, 7 or 14. RESULTS: Peritoneal dissemination score was significantly higher in the laparotomy group compared with in the remaining three groups on PODs 2 and 7. We detected no significant differences in the peritoneal dissemination scores among the low-IPP, high-IPP, and anesthesia groups on PODs 2 and 7. However, there were no significant differences in the peritoneal dissemination score among the three surgical groups on POD 14. Histopathological examination demonstrated that the incidence of invasion of cancer cells into the muscle layers was significantly higher in the laparotomy group than in the low-IPP and anesthesia groups on POD 14. There were no significant differences in tumor growth among the four groups. CONCLUSIONS: The present findings suggest that CO(2) pneumoperitoneum at either high or low IPP has few if any short-term effects on peritoneal dissemination when tumors are well established before surgery.