Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC. PATIENTS AND METHODS: Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC. RESULTS: Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates (P < .0001) and 3-year overall survival (OS) rates (P < .0001). TNBC was associated with increased risk for visceral metastases (P = .0005), lower risk for bone recurrence (P = .027), and shorter postrecurrence survival (P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival (P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC (P < .0001). CONCLUSION: Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.

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.

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.

Axillary reverse mapping using near-infrared fluorescence imaging in invasive breast cancer (ARMONIC study).

BACKGROUND: Axillary lymph node dissection (ALND) in patients with breast cancer has potential side effects, including upper-limb lymphedema. Axillary reverse mapping (ARM) is a technique that enables discrimination of the lymphatic drainage of the upper limb in the axillary lymph node basin from that of the breast. We aimed to evaluate ARM node identification by near-infrared (NIR) fluorescence imaging during total mastectomy with ALND and then to analyze potential predictive factors of ARM node involvement. METHODS: The study enrolled 119 patients diagnosed with invasive breast cancer with an indication for ALND. NIR imaging using indocyanine green dye was performed in 109 patients during standard ALND to identify ARM nodes and their corresponding lymphatic ducts. RESULTS: 94.5% of patients had ARM nodes identified (95%CI = [88.4-98.0]). The ARM nodes were localized in zone D in 63.4% of cases. Metastatic axillary lymph nodes were found in 55% in the whole cohort, and 19.4% also had metastasis in ARM nodes. Two patients had metastatic ARM nodes but not in the remaining axillary lymph nodes. No serious adverse events were observed. Only the amount of mitosis was significantly associated with ARM node metastasis. CONCLUSIONS: ARM by NIR fluorescence imaging could be a reliable technique to identify ARM nodes in real-time when ALND is performed. The clinical data compared with ARM node histological diagnosis showed only the amount of mitosis in the diagnostic biopsy is a potential predictive factor of ARM node involvement. CLINICAL TRIAL REGISTRATION: NCT02994225.

Near-Infrared Fluorescence Axillary Reverse Mapping (ARM) Procedure in Invasive Breast Cancer: Relationship between Fluorescence Signal in ARM Lymph Nodes and Clinical Outcomes.

The near-infrared (NIR) fluorescence axillary reverse mapping (ARM) procedure is a promising tool to identify and preserve arm lymphatic drainage during axillary lymph node dissection (ALND). The ARMONIC clinical trial was conducted to validate the technique on a large cohort of patients and to analyze the predictive clinical factors for ARM lymph node metastasis. For the first time, the fluorescence signal intensity from the ARM lymph nodes was measured and correlated with clinical findings. A total of 109 patients with invasive breast cancer and indications of mastectomy and ALND underwent the NIR fluorescence ARM procedure. Indocyanine green was administered by intradermal injection followed by intraoperative identification and resection of the ARM lymph nodes with NIR fluorescence camera guidance. The fluorescence signal intensity and signal distribution were then measured ex vivo and compared with clinical outcomes. ARM lymph nodes were successfully identified by fluorescence in 94.5% of cases. The mean normalized fluorescence signal intensity value was 0.47 with no significant signal difference between metastatic and non-metastatic ARM lymph nodes (p = 0.3728). At the microscopic level, the fluorescence signal distribution was focally intense in lymphoid tissue areas. Only the preoperative diagnosis of metastasis in the axillary nodes of patients was significantly associated with a higher ARM node fluorescence signal intensity (p = 0.0253), though it was not significantly associated with the pathological nodal (pN) status (p = 0.8081). Based on an optimal cut-off fluorescence value, the final sensitivity and specificity of the NIR fluorescence ARM procedure for ARM lymph node metastatic involvement were 64.7% and 47.3%, respectively. Although our preliminary results did not show that fluorescence signal intensity is a reliable diagnostic tool, the NIR fluorescence ARM procedure may be useful for ARM lymph node identification. Clinical trial registration: NCT02994225.

Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions.

BACKGROUND: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting. - METHODS: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model. RESULTS: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers. CONCLUSION: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH. CLINICAL TRIAL REGISTRATION: NCT02523612.

Adipose Tissue Properties in Tumor-Bearing Breasts.

The tissue stroma plays a major role in tumors' natural history. Most programs for tumor progression are not activated as cell-autonomous processes but under the conditions of cross-talks between tumor and stroma. Adipose tissue is a major component of breast stroma. This study compares adipose tissues in tumor-bearing breasts to those in tumor-free breasts with the intention of defining a signature that could translate into markers of cancer risk. In tumor-bearing breasts, we sampled adipose tissues adjacent to, or distant from the tumor. Parameters studied included: adipocytes size and density, immune cell infiltration, vascularization, secretome and gene expression. Adipose tissues from tumor-bearing breasts, whether adjacent to or distant from the tumor, do not differ from each other by any of these parameters. By contrast, adipose tissues from tumor-bearing breasts have the capacity to secrete twice as much interleukin 8 (IL-8) than those from tumor-free breasts and differentially express a set of 137 genes of which a significant fraction belongs to inflammation, integrin and wnt signaling pathways. These observations show that adipose tissues from tumor-bearing breasts have a distinct physiological status from those from tumor-free breasts. We propose that this constitutive status contributes as a non-cell autonomous process to determine permissiveness for tumor growth.

Pregnancy after Breast Reconstruction.

Breast cancer is one of the most commonly diagnosed malignancies in women of childbearing age. One of the surgeries performed in the management of the disease is mastectomy , which might negatively affect body image and quality of life, and breast reconstruction is seen as a remedy to this problem. However, for the women who are interested in having children after treatment of breast cancer, the debate is whether they can have a successful pregnancy and delivery after breast reconstruction.

Imperfect biomarkers for adjuvant chemotherapy in early stage breast cancer with good prognosis.

The proliferation of biomarkers has raised concerns regarding the possibility for clinical judgment to be improperly removed from clinician's jurisdiction and included in laboratory tests. To evaluate the ways in which the diffusion of biomarkers questions the autonomy of clinicians, we consider the case of chemotherapy prescription to women with early stage breast cancer and a good prognosis. Drawing on a qualitative study of clinicians working in a diversity of institutional contexts, we follow three biomarkers available to guide this routinely made decision. We show that, biomarkers able to reduce all the uncertainties associated with, what we analyse as an uncomfortable decision, are sought more than dreaded by clinicians. If such ideal tools are unavailable, the fact is well acknowledged by the profession. Rather than precluding their usage, the imperfection of existing biomarkers is controlled by the profession, through their integration as additional tools in the decision process. The fact that the biomarkers are recognized as imperfect biomedical entities reinforces the importance of local material, organizational and financial constraints over that of international science, technology and clinical data, in their diffusion. The regulation of the uncertainties associated with these imperfections is organized at the professional level. Through an important work, relying on guidelines and enforced in collective bodies, the series of heterogeneous bioclinical evidences available are articulated. Biomarkers tend to be subordinated to the clinic. While maintaining the professional autonomy, the process also strengthens the internal professional hierarchy. When the most expert clinicians manage to inhabit a space for clinical autonomy, the nonexpert are torn between stronger professional rules and patient preferences. In this alliance between biomarkers and experts, their clinical autonomy tends to be the price for the professional autonomy.

Near-infrared fluorescence imaging for the prevention and management of breast cancer-related lymphedema: A systematic review.

Sentinel lymph node identification by near infrared (NIR) fluorescence with indocyanine green (ICG) is recognized in the literature as a useful technique. NIR fluorescence technology could become key in the prevention and management of lymphedema after axillary dissection for breast cancer. Here, we conducted a systematic review focusing on ICG imaging to improve lymphedema prevention and treatment after axillary surgery. A systematic literature review was performed using MEDLINE and Embase to identify articles focused on ICG imaging for breast-cancer-related lymphedema (BCRL). Qualitative analysis was performed to summarize the characteristics of reported ICG procedures. In situ tissue identification and functionality assessment based on fluorescence signal were evaluated. Clinical outcomes were appraised when reported. Studies relating to axillary reverse mapping, lymphography and upper limb supermicrosurgery combined with ICG imaging were identified. We included a total of 33 relevant articles with a total of 2016 patients enrolled. ICG imaging for axillary reverse mapping was safe for all 951 included patients, with identification of arm nodes in 80%-88% of patients with axillary lymph nodes dissection. However, the papers discuss the oncologic safety of the approach and how - regardless of the contrast agent - concerns limit its adoption. ICG lymphography is openly supported in BCRL management, with 1065 patients undergoing this procedure in 26 articles. The technique is reported for lymphedema diagnosis, with high sensitivity and specificity, staging, intraoperative mapping and patency control in lymphaticovenular anastomosis. The substantial advantages/disadvantages of ICG imaging procedures are finally described.

Tubular and mucinous breast cancer: results of a cohort of 917 patients.

OBJECTIVES:: To analyze axillary lymph node involvement (ALNI) rate and survival for mucinous (MC) and tubular (TC) breast carcinomas considered being of very good prognosis and for which an axillary surgical exploration could be questioned. METHODS:: Our multicentric cohort consisted of 21,135 patients with clinically node-negative invasive breast cancer, without neoadjuvant therapy, between 1999 and 2013 in 10 French centers. ALNI rate and survival were analyzed according to patient and tumor characteristics. RESULTS:: Our cohort consisted of 672 TC and 245 MC. Patients were older and tumor size greater for MC and pathologic factors were more pejorative. The rate of mastectomies and adjuvant chemotherapy was higher in the MC group. Axillary lymph node status was determined by SLNB alone in 71.2% of patients. ALNI rates were 17.9% and 18% for TC and MC, respectively. ALNI rate was lesser for MC (OR 0.503, p = 0.024) and greater in case of lympho-vascular invasion (OR 5.0, p < 0.0001) and for tumors >10 mm (OR 2.17, p = 0.042). Median follow-up was 58 months. The 5- and 7-year overall survival rates were 97.1% and 95% for TC, respectively; 92.3% and 91.2% for MC ( p = 0.043); 5- and 7-year disease-free survival rates were 97.9% and 97.2% versus 95.2 and 93.6% ( p = 0.041). Lympho-vascular invasion was the only predictive factor for overall survival (hazard ratio [HR] = 2.70)' grade 2 (HR = 10) and HR-negative (HR = 4.9) were the two predictive factors for disease-free survival. CONCLUSION:: This study confirms the need for an axillary exploration for these tumors even for a tumor size <10 mm and a favorable prognosis.

Preoperative Breast Magnetic Resonance Imaging in Women With Local Ductal Carcinoma in Situ to Optimize Surgical Outcomes: Results From the Randomized Phase III Trial IRCIS.

PURPOSE: We evaluated the addition of breast magnetic resonance imaging (MRI) to standard radiologic evaluation on the re-intervention rate in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery. PATIENTS AND METHODS: Women with biopsy-proven DCIS corresponding to a unifocal microcalcification cluster or a mass less than 30 mm were randomly assigned to undergo MRI or standard evaluation. The primary end point was the re-intervention rate for positive or close margins (< 2 mm) in the 6 months after randomization ( ClinicalTrials.gov identifier: NCT01112254). RESULTS: A total of 360 patients from 10 hospitals in France were included in the study. Of the 352 analyzable patients, 178 were randomly assigned to the MRI arm, and 174 were assigned to the control arm. In the intent-to-treat analysis, 82 of 345 patients with the assessable end point were reoperated for positive or close margins within 6 months, resulting in a re-intervention rate of 20% (35 of 173) in the MRI arm and 27% (47 of 172) in the control arm. The absolute difference of 7% (95% CI, -2% to 16%) corresponded to a relative reduction of 26% (stratified odds ratio, 0.68; 95% CI, 0.41 to 1.1; P = .13). When considering only the per-protocol population with an assessable end point, the difference was 9% (stratified odds ratio, 0.59; 95% CI, 0.35 to 1.0; P = .05). Total mastectomy rates were 18% (31 of 176) in the MRI arm and 17% (30 of 173) in the control arm (stratified P = .93). For 100 lesions seen on MRI, nonmass-like enhancement was more predominant (82%) than mass enhancement (20%). Nevertheless, no specific morphologic and kinetic parameters for DCIS were identified. CONCLUSION: The study did not show sufficient surgical improvement with the use of preoperative MRI to be clinically relevant in DCIS staging. However, this could be reconsidered with the improvement of new MRI sequences and new modalities in magnetic resonance techniques.

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.

Clinical Response to Induction Chemotherapy Predicts Outcome after Combined-Modality Therapy in Inflammatory Breast Cancer.

PURPOSE: To assess predictors of outcome in a cohort of Inflammatory Breast Cancer (IBC) patients receiving induction chemotherapy followed by local treatment. METHODS: We retrospectively reviewed 95 non-metastatic IBC patient files. RESULTS: Complete clinical response (cCR) was obtained in 15 (16%) patients. Median follow up was 13.4 years (IC95%: 10.4-14.6). Loco-regional control (LC), disease-free survival (DFS), and overall survival (OS) at 5 years were 85%, 41%, and 55%, respectively; cCR was associated with better DFS and OS in multivariate analyses adjusted for age (p = 0.02). CONCLUSIONS: Clinical response to upfront chemotherapy predicts the outcome of patients affected by IBC.

Lymph node positivity in different early breast carcinoma phenotypes: a predictive model.

BACKGROUND: A strong correlation between breast cancer (BC) molecular subtypes and axillary status has been shown. It would be useful to predict the probability of lymph node (LN) positivity. OBJECTIVE: To develop the performance of multivariable models to predict LN metastases, including nomograms derived from logistic regression with clinical, pathologic variables provided by tumor surgical results or only by biopsy. METHODS: A retrospective cohort was randomly divided into two separate patient sets: a training set and a validation set. In the training set, we used multivariable logistic regression techniques to build different predictive nomograms for the risk of developing LN metastases. The discrimination ability and calibration accuracy of the resulting nomograms were evaluated on the training and validation set. RESULTS: Consecutive sample of 12,572 early BC patients with sentinel node biopsies and no neoadjuvant therapy. In our predictive macro metastases LN model, the areas under curve (AUC) values were 0.780 and 0.717 respectively for pathologic and pre-operative model, with a good calibration, and results with validation data set were similar: AUC respectively of 0.796 and 0.725. Among the list of candidate's regression variables, on the training set we identified age, tumor size, LVI, and molecular subtype as statistically significant factors for predicting the risk of LN metastases. CONCLUSIONS: Several nomograms were reported to predict risk of SLN involvement and NSN involvement. We propose a new calculation model to assess this risk of positive LN with similar performance which could be useful to choose management strategies, to avoid axillary LN staging or to propose ALND for patients with high level probability of major axillary LN involvement but also to propose immediate breast reconstruction when post mastectomy radiotherapy is not required for patients without LN macro metastasis.

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.

Individualized Prediction of Menses Recovery After Chemotherapy for Early-stage Breast Cancer: A Nomogram Developed From UNICANCER PACS04 and PACS05 Trials.

BACKGROUND: The likelihood of menses recovery varies greatly in premenopausal patients receiving adjuvant chemotherapy for breast cancer. Quantifying this probability for each patient could better inform the chemotherapy discussion and individualize fertility counseling. We performed a pooled analysis of the PACS04 and PACS05 adjuvant randomized trials to develop a nomogram to estimate the probability of menses recovery at 3, 6, and 18 months after the end of adjuvant chemotherapy. PATIENTS AND METHODS: Women who were premenopausal and aged ≤ 50 years at randomization in the PACS04 and PACS05 trials were included in the present analysis. The primary endpoint was the probability of menses recovery within 18 months of chemotherapy completion. Multivariable Cox proportional hazards regression was used to estimate the association of each variable with the likelihood of menses resumption. A nomogram was developed to predict menses recovery at different intervals. RESULTS: The factors associated with menses recovery were assessed for 1210 patients. At a median follow-up of 90 months (range, 3-189 months), 342 of 1210 patients (28.2%) had recovered menses. The probability of menses recovery at 18 months was 25.5% (range, 23.0%-27.9%). After backward elimination, age, final body mass index, type of chemotherapy, and hormone therapy were selected to build the nomogram to predict the probability of menstrual resumption at 3, 6, and 18 months after chemotherapy. CONCLUSION: An accurate and individualized prediction of menses recovery is feasible for premenopausal patients eligible for adjuvant chemotherapy for early-stage breast cancer. Our nomogram will be externally validated in a large prospective cohort.

Survival Impact of Locoregional Treatment of the Primary Tumor in De Novo Metastatic Breast Cancers in a Large Multicentric Cohort Study: A Propensity Score-Matched Analysis.

INTRODUCTION: Improvement in overall survival (OS) by locoregional treatment (LRT) of the primary tumor in de novo metastatic breast cancer (MBC) patients remains controversial. OBJECTIVE: The aim of our study was to evaluate the impact of LRT on OS in a large retrospective cohort of de novo MBC patients, with regard to immunohistochemical characteristics and pattern of metastatic dissemination. METHODS: We conducted a multicentric retrospective study of patients diagnosed with de novo MBC selected from the French Epidemiological Strategy and Medical Economics MBC database (NCT03275311) between 2008 and 2014. Overall, 4276 women were included in the study. LRT comprised either radiotherapy, surgery, or both. RESULTS: LRT was used in 40% of patients. Compared with no LRT, patients who received LRT were younger (p < 0.0001) and were more likely to have only one metastatic site (p < 0.0001) or bone-only metastases (p < 0.0001). LRT was associated with a significantly better OS based on landmark multivariate analysis at 1-year (hazard ratio 0.65, 95% confidence interval 0.55-0.76, p < 0.001). Similar results were observed in all sensitivity analyses, including propensity score matching. In subgroup analysis, LRT was associated with better OS in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (61.6 vs. 45.9 months, p < 0.001) and HER2-positive tumors (77.2 vs. 52.6 months, p = 0.008), but not in triple-negative tumors (19 vs. 18.6 months, p = 0.54), and was also associated with a reduction in the risk of death in visceral metastatic patients (p < 0.001). CONCLUSIONS: LRT was associated with a significantly better OS in de novo MBC patients, including patients with visceral involvement at diagnosis; however, LRT did not impact OS in triple-negative MBC.