[Surgery or not on an atypical breast lesion? Taking anxiety into account in shared decision support from a prospective cohort of 300 patients]. / Opérer ou non une lésion atypique du sein ? Prise en compte de l'anxiété dans l'aide à la décision partagée à partir d'une cohorte prospective de 300 patientes.

INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.

Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study.

BACKGROUND: We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors. PATIENTS AND METHODS: We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the Kaplan-Meier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients. RESULTS: LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients [hazard ratio (HR) = 1.345, HR = 1.312, and HR = 1.415, respectively; P < 0.0001], which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with AC-treated luminal A-like tumors. CONCLUSION: The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy.

Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort☆.

BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm. PATIENTS AND METHODS: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status. RESULTS: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS. CONCLUSION: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.

[Comparing outcomes of Immediate Breast reconstruction with and without use of radiotherapy]. / Comparaison des résultats de reconstruction mammaire immédiate par prothèse avec et sans radiothérapie.

BACKGROUND: Breast cancer and its treatment remains a public health problem. There is still a lack of epidemiological data concerning complications and aesthetic results bound to radiotherapy after an immediate breast reconstruction. The objective of this study was to compare outcomes of immediate breast reconstruction regardless to the use of radiotherapy (history of radiotherapy or adjuvant radiation therapy), in order to determine risk factor of complications and bad aesthetic results. METHODS: We conducted a retrospective study between January 2014 and December 2016 at the hospital "Gustave Roussy" in Paris, concerning breast cancer patients who needed immediate breast reconstruction after total mastectomy. The primary endpoint was to assess the failure rate of reconstruction and the aesthetic result, the secondary endpoint assessed the early and late rate of complications. We realized a multivariate analysis in order to identify risks factors that may predict complications. RESULTS: Three hundred and thirty three patients have been included: 157 in the "radiotherapy group" compared to 176 in the "no radiotherapy group". Preoperative characteristics were comparable. Average follow-up was between 1 and 3years without missing. Patients who benefited from radiotherapy had an equal risk failure of reconstruction. The subgroup analysis revealed non-significant differences: 12.7% failure rate reconstruction in the "radiotherapy group" vs. 12.5%. We could notify a better rate of "excellent results" in the "no radiotherapy group": 35% vs. 8.2%. Secondary outcomes were comparable. CONCLUSIONS: Radiotherapy related to immediate breast reconstruction didn't increase the failure rate of reconstruction or aesthetic results, comparatively to non-irradiated patients. It is therefore permissible to suggest an immediate breast reconstruction to any patients which would benefit from a total mastectomy followed by radiotherapy; in order to prevent them from a secondary breast reconstruction, who could be physically and psychologically more impactful.

[Decision algorithm in immediate breast reconstruction]. / Algorithmes décisionnels en reconstruction mammaire immédiate.

Immediate breast reconstruction showed many advantages in terms of aesthetic and functional results and improvement of quality of life when compared to delayed breast reconstruction. Previous radiotherapy or the use of adjuvant treatments such as radiation therapy, or chemotherapy are no longer a contraindication for immediate breast reconstruction. However, it is important to respect certain rules in order to decrease the risk of complications: the choice of reconstruction technique, the management of the skin envelope according to the breast shape you want to create, the time delay between the first and the second stage of reconstruction depending on a possible adjuvant treatment.

[Mastectomy and immediate reconstruction: Indications, techniques and decision algorithm]. / Mastectomie avec reconstruction mammaire immédiate : indications et techniques, algorithme de décision d'une reconstruction immédiate.

Immediate breast reconstruction indications extend to infiltrating carcinomas, due to new matrix implant coverage techniques and the development of perforator flaps. These techniques allow adjuvant treatments. However, the decision of immediate reconstruction must be discussed with the oncological multidisciplinary team and the benefits/risks must also be evaluated in relation to the morphology of the patients and their co-morbidities. The chosen type of mastectomy: conventional or skin sparing and/or nipple sparing depends on the shape and volume of the breast, the localization of the tumor in the breast and the distance from the nipple areola complex (NAC). We describe an algorithm to allow, in the case of therapeutic mastectomy with or without adjuvant radiotherapy, an immediate reconstruction with implants or free or pedicled flaps.

Modulation of Rb phosphorylation and antiproliferative response to palbociclib: the preoperative-palbociclib (POP) randomized clinical trial.

Background: The cyclin-dependent kinase 4 (CDK4)/6 inhibitor Palbociclib is a new standard treatment in hormone-receptor positive breast cancer patients. No predictive biomarkers have been identified and no pharmacodynamics has properly been described so far. Patients and methods: Patients with early-breast cancer were randomized 3 : 1 to oral palbociclib 125 mg daily for 14 days until the day before the surgery versus no treatment. Primary objective was antiproliferative response defined as a natural logarithm of Ki67 expression at day 15 below 1. Secondary end points were subgroups analyses and safety. Exploratory analyses included search for predictive biomarkers. Immunostainings (Ki67, RB, pRB, p16, pAKT, pER, pCDK2, CyclinD1), FISH (CCND1) and gene expression (GE) arrays were carried out at baseline and at surgery. In addition, activating PIK3CA and AKT1 mutations were assessed at baseline. Results: 74 patients were allocated to palbociclib and 26 to control. Most patients (93%) were hormone-receptor (HR)-positive, whereas 8% were HER2-positive. Palbociclib led to significantly more antiproliferative responses when compared with control (58% versus 12%, P < 0.001), and to a significantly higher Ki67 decrease (P < 0.001). In the HR-positive/HER2-negative subgroup, this antiproliferative effect was even more marked in the palbociclib arm when compared with control (70% versus 9%, P < 0.001). Palbociclib treatment led also to a significantly higher decrease from baseline in phospho-Rb when compared with control (P < 0.001). Among treated patients, changes in Ki67 correlated with changes in phospho-Rb (Spearman rank r = 0.41, P < 0.0001). GE analyses confirmed a major effect on proliferation and cell cycle genes. Among treated patients, CCNE2 expression was significantly more decreased in antiproliferative responders versus nonresponders (P = 0.006). Conclusion: Short-term preoperative palbociclib decreases Ki67 in early-breast cancer patients. Early decrease of Rb phosphorylation correlates with drug's effect on cell proliferation and could potentially identify patients with primary resistance. Clinical trial registration: NCT02008734.

[Use of indocyanine green angiography in oncological and reconstructive breast surgery]. / Utilisation du vert d'indocyanine en chirurgie sénologique et reconstruction mammaire.

The Indocyanine green (ICG) is a soluble dye that is eliminated by the liver and excreted in bile. When illuminated by an near-infrared light, the ICG emits fluorescence in the near-infrared spectrum, which can be captured by a near-infrared camera-handled device. In case of intravenous injection, ICG may be used as a marker of skin perfusion. In case of interstitial injection, it may be useful for lymphatic network mapping. In oncological and reconstructive breast surgery, ICG is used for sentinel lymph node identification, to predict mastectomy skin flap necrosis, to assess the perfusion of free flaps in autologous reconstruction and for diagnosis and treatment of upper limb secondary lymphedema. Intraoperative indocyanine green fluorescence might also be used to guide the excision of nonpalpable breast cancer.

Preoperative radiotherapy in breast cancer patients: 32 years of follow-up.

This study evaluates the long-term outcomes of a retrospective cohort of breast cancer (BC) patients who had received curatively intended premastectomy radiation therapy (RT). We analysed locoregional control, disease-free survival (DFS) and overall survival (OS), pathological complete remission (pCR), predictors thereof, and immediate safety. The series consisted of 187 patients with a median age of 49 years [43-60] and T2-T4 or N2 tumours. Between 1970 and 1984, they had received slightly hypofractionated RT to the whole breast, ipsilateral supraclavicular fossa and axilla ± the internal mammary chain (45-55 Gy/18 fractions of 2.5 Gy/34 days) systematically followed by a modified radical mastectomy with an axillary dissection. No other preoperative treatment was given. Among the 166 centrally reviewed tumour biopsy specimens, 22% had a triple-negative (TN) phenotype, 17% were HER2 3 + or amplified and 61% were ER+. The median follow-up was 32 years [23-35]. The 25-year locoregional control rate was 89% [93%-82%] and the 25-year DFS and OS rates were identical, 30% [24%-37%]. A pCR in the tumour and lymph nodes had been achieved in 18 among all patients (10%), but in 26% with TN disease. In the multivariate analysis, the TN status was the only predictive factor of pCR (OR = 5.49, 95% confidence interval [CI] 1.87-16.1, p = 0.002). Also, the pN status (HR = 1.69, [1.28-2.22], p = 0.0002) and TN subtype (HR = 1.80, [1.00-3.26], p = 0.05) exerted a significant prognostic impact on OS. The postoperative complication rate (grade >2) was 19% with 4.3% of localized skin necrosis. Preoperative RT followed by radical surgery is feasible and associated with good long-term locoregional control.

Variation in rates of breast cancer surgery: A national analysis based on French Hospital Episode Statistics.

AIMS: Minimum volume thresholds were introduced in France in 2008 to improve the quality of cancer care. We investigated whether/how the quality of treatment decisions in breast cancer surgery had evolved before and after this policy was implemented. METHODS: We used Hospital Episode Statistics for all women having undergone breast conserving surgery (BCS) or mastectomy in France in 2005 and 2012. Three surgical procedures considered as better treatment options were analyzed: BCS, immediate breast reconstruction (IBR) and sentinel lymph node biopsy (SLNB). We studied the mean rates and variation according to the hospital profile and volume. RESULTS: Between 2005 and 2012, the volume of breast cancer surgery increased by 11% whereas one third of the hospitals no longer performed this type of surgery. In 2012, the mean rate of BCS was 74% and similar in all hospitals whatever the volume. Conversely, IBR and SLNB rates were much higher in cancer centers (CC) and regional teaching hospitals (RTH) [IBR: 19% and 14% versus 8% on average; SLNB: 61% and 47% versus 39% on average]; the greater the hospital volume, the higher the IBR and SLNB rates (p < 0.0001). Overall, whatever the surgical procedure considered, inter-hospital variation in rates declined substantially in CC and RTH. CONCLUSIONS: We identified considerable variation in IBR and SLNB rates between French hospitals. Although more complex and less standardized than BCS, most clinical guidelines recommended these procedures. This apparent heterogeneity suggests unequal access to high-quality procedures for women with breast cancer.

Toward a new strategy in desmoid of the breast?

AIM: To report initial results of observation as well as surgery in patients with desmoid tumors (DTs) of the breast, a rare tumor for which data are scarce. PATIENTS AND METHODS: The initial approaches were categorized as either front-line loco-regional treatment [(surgery or radiotherapy group, SRG) n = 20] or initial observation [(no surgery/no radiotherapy group, NSRG) n = 11]. RESULTS: A total of 27 women and 4 men were assessed between 1992 and 2013 and included in this study. Patient characteristics were adequately balanced in the 2 groups. Fifteen patients (48.4%) had a past history of breast surgery in the previous 24 months. The median initial DT size on MRI was 50 mm. The median follow-up was 36 months. In the SRG, 8/20 patients (40%) experienced recurrence. The median time to recurrence was 29 months. During the study period, 6 patients in the SRG (30%) received a mastectomy at the time of diagnosis (n = 3) or at relapse (n = 3), 7 patients (35%) received a thoracic wall resection and 8 patients (40%) received radiotherapy at the time of diagnosis (n = 2) or at recurrence (n = 5). In the NSRG, the median tumor size change was -4 mm (range -13 to +20). Three patients changed treatment strategies during the observation period; one received surgery, and 2 were administered anti-hormonal treatment. CONCLUSIONS: Loco-regional treatments of breast DTs resulted in undesired disfigurement. Front-line observation yielded encouraging results and could enable the identification of patients who require loco-regional treatment. This strategy needs further evaluation.

A preoperative nomogram to predict the risk of synchronous distant metastases at diagnosis of primary breast cancer.

BACKGROUND: The detection of synchronous metastases at primary diagnosis of breast cancer (BC) affects its initial management. A risk calculator that incorporates many factors to evaluate an individual's risk of harbouring synchronous metastases would be useful to adapt cancer management. PATIENTS AND METHODS: Patients with primary diagnosis of BC were identified from three institutional databases sharing homogeneous work-up recommendations. A risk score for synchronous metastases was estimated and a nomogram was constructed using the first database. Its performance was assessed by receiver characteristic (ROC) analysis. The nomogram was externally validated in the two independent cohorts. RESULTS: A preoperative nomogram based on the clinical tumour size (P<0.001), clinical nodal status (P<0.001), oestrogen (P=0.17) and progesterone receptors (P=0.04) was developed. The nomogram accuracy was 87.3% (95% confidence interval (CI), 84.45-90.2%). Overall, the area under the ROC curve (AUC) was 86.1% for the validation set from the Institut Curie-René Huguenin, and 63.8% for the MD Anderson validation set. The negative predictive value (NPV) was high in the three cohorts (97-99%). CONCLUSIONS: We developed and validated a strong metastasis risk calculator that can evaluate with high accuracy an individual's risk of harbouring synchronous metastases at diagnosis of primary BC. CONDENSED ABSTRACT: A nomogram to predict synchronous metastases at diagnosis of breast cancer was developed and externally validated. This tool allows avoiding unnecessary expensive work-up.

Should BRCA2 mutation carriers avoid neoadjuvant chemotherapy?

BRCA2 mutation carriers typically develop luminal B breast cancers. Data on the effectiveness of neoadjuvant chemotherapy in these patients are limited because of small patient numbers and lack of prospective studies. We used our 15-year genetic clinic database to compare retrospectively the pathological complete response rates (pCR) and rates of post-chemotherapy nodal involvement among BRCA2 carriers and BRCA1/2-negative (WT) patients with luminal B tumours, all treated with neoadjuvant anthracyclines±taxanes-based chemotherapy. Twenty-nine BRCA2 carriers and 67 WT patients fulfilled the inclusion criteria and were analysed. Patients and treatment characteristics were represented. A pCR occurred in 3 (10%) BRCA2 patients and 13 (19%) WT patients (p=0.43). Twenty (69%) BRCA2 carriers and 34 (51%) WT patients remained node-positive at surgery (p=0.17). BRCA2 germline mutations are associated with a low probability of pCR and a high risk of axillary invasion. Alternative treatments are highly expected, and clinical trials are needed to set the best treatment regimen in this population.

Pure and mixed mucinous carcinoma of the breast: fine needle aspiration cytology findings and review of the literature.

OBJECTIVE: Mucinous (colloid) breast carcinoma accounts for 1-6% of all breast cancer. It comprises pure mucinous tumours and mixed infiltrating ductal carcinomas with a mucinous component. As this latter mixed form has a worse prognosis than pure colloid carcinoma, making this diagnosis on fine needle aspiration cytology (FNAC) might influence the choice of treatment. METHODS: We report a consecutive series of 22 cases consisting of 17 mixed and five pure mucinous carcinomas diagnosed by cytology and verified on histopathology. Patients underwent FNAC at the one-stop clinic of our institution during a 7-year period of time. Cytological findings were evaluated by a semi-quantitative method and included percentage of smear surface occupied by mucin, shape of cell groupings, size and outline of tumour nuclei as well as presence or absence of nucleolus. RESULTS: Three of five pure mucinous carcinomas displayed at least two of the following features: abundant mucin, small nuclei and/or regular nuclear outlines. Sparse mucin, large nuclei, irregular nuclear outlines or the presence of nucleoli were found in 7 out of 17 mixed mucinous carcinomas but not in pure tumours. CONCLUSION: Cytopathological identification of patients with pure mucinous carcinomas may be performed in a limited number of cases.

A nomogram to predict individual prognosis in node-negative breast carcinoma.

BACKGROUND: Currently, the benefit of chemotherapy (CT) in node-negative breast carcinoma (NNBC) is discussed. The evaluation of classical clinical and histological factors is limited to assess individual outcome. A statistical model was developed to improve the prognostic accuracy of NNBC. METHODS: A total of 305 node-negative breast carcinomas who underwent surgery (+/- radiotherapy) but no adjuvant treatment were selected. Putative prognosis factors including age, tumour size, oestrogen receptor (ER), progesterone receptor (PgR), Scarff-Bloom-Richardon (SBR) grading, urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) and thymidine kinase (TK) were evaluated. The developed model was internally validated using Harrell's concordance index. A prognosis index (PI) was proposed and compared with Adjuvant! Online program. RESULTS: Age (p < 0.001), pathological tumour size (pT) (p < 0.001), PgR (p = 0.02), and PAI-1 (p ≤ 0.001) were included in the Cox regression model predicting Breast cancer specific survival (BCSS) at 5-years. Internal validation revealed a concordance index of 0.71. A PI score was derived from our nomogram. The PI score was significantly associated with BCSS (hazard ratio (HR): 4.1 for intermediate, p=0.02, HR: 8.8, p < 0.001 for high group) as compared to Adjuvant! Online score (HR: 1.4, p=0.14). CONCLUSION: A nomogram can be used to predict probability survival curves for individual breast cancer patients.

Breast Cancer Index predicts pathological complete response and eligibility for breast conserving surgery in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: The aim of neoadjuvant chemotherapy is to increase the likelihood of successful breast conservation surgery (BCS). Accurate identification of BCS candidates is a diagnostic challenge. Breast Cancer Index (BCI) predicts recurrence risk in estrogen receptor+lymph node-breast cancer. Performance of BCI to predict chemosensitivity based on pathological complete response (pCR) and BCS was assessed. METHODS: Real-time RT-PCR BCI assay was conducted using tumor samples from 150 breast cancer patients treated with neoadjuvant chemotherapy. Logistical regression and c-index were used to assess predictive strength and additive accuracy of BCI beyond clinicopathologic factors. RESULTS: BCI classified 42% of patients as low, 35% as intermediate and 23% as high risk. Low BCI risk group had 98.4% negative predictive value (NPV) for pCR and 86% NPV for BCS. High versus low BCI group had a 34 and 5.8 greater likelihood of achieving pCR and BCS, respectively (P=0.0055; P=0.0022). BCI increased c-index for pCR (0.875-0.924; P=0.017) and BCS prediction (0.788-0.843; P=0.027) beyond clinicopathologic factors. CONCLUSIONS: BCI significantly predicted pCR and BCS beyond clinicopathologic factors. High NPVs indicate that BCI could be a useful tool to identify breast cancer patients who are not eligible for neoadjuvant chemotherapy. These results suggest that BCI could be used to assess both chemosensitivity and eligibility for BCS.

Epstein-Barr virus as a marker of biological aggressiveness in breast cancer.

PURPOSE: Although a potential role of the Epstein-Barr virus (EBV) in the pathogenesis of breast cancer (BC) has been underlined, results remain conflicting. Particularly, the impact of EBV infection on biological markers of BC has received little investigation. METHODS: In this study, we established the frequency of EBV-infected BC using real-time quantitative PCR (RT-PCR) in 196 BC specimens. Biological and pathological characteristics according to EBV status were evaluated. RESULTS: EBV DNA was present in 65 of the 196 (33.2%) cases studied. EBV-positive BCs tended to be tumours with a more aggressive phenotype, more frequently oestrogen receptor negative (P=0.05) and with high histological grade (P=0.01). Overexpression of thymidine kinase activity was higher in EBV-infected BC (P=0.007). The presence of EBV was weakly associated with HER2 gene amplification (P=0.08). CONCLUSION: Our study provides evidence for EBV-associated BC undergoing distinct carcinogenic processes, with more aggressive features.

[Indications and technical procedures of mastectomy with immediate breast reconstruction]. / Indications, conditions de réalisation et techniques de la mastectomie avec reconstruction immédiate dans le cancer du sein.

Achieving a mastectomy occurs in one third of the acts of breast cancer surgery. In the present context, the increase in the diagnosis of early breast cancer, including widespread or multifocal forms, the possibility of a reconstruction at the same time is discussed. It will be proposed in a specific context, taking into account various factors: oncological (characteristics of the tumor, adjuvant treatments), clinical (smoking, comorbidity) and psychological (choice of the patient). The technique of mastectomy will be adapted to the indication and choice of reconstruction procedure. Including the preservation of the nipple-areola complex, or the skin envelope will be possible for some guidance. The reconstruction is possible with the use of breast implants, or musculocutaneous flaps or by the combination of both. Some of these techniques are associated with significant morbidity, and appropriate selection of procedure to the patient will guarantee a lower risk of complications.

Collagen IV levels are elevated in the serum of patients with primary breast cancer compared to healthy volunteers.

Collagen IV is a major component of the vascular basement membrane and may be a marker of angiogenesis. Serum levels of this protein are elevated in some human cancers. Our objectives were to compare collagen IV levels in the serum of breast cancer patients and healthy women and to examine changes during preoperative chemotherapy. Sera from 51 patients with stage II-III breast cancer and 55 healthy controls were analysed. Collagen IV level was measured by a commercially available sandwich enzyme link immunoassay. Baseline serum levels were compared between cancer patients and healthy women and paired pre- and post-chemotherapy measurements were also performed in 39 patients who received preoperative chemotherapy and were correlated with response to therapy. The median serum collagen IV concentration was significantly higher in cancer patients (166 microg l(-1)) than in healthy women (115 microg l(-1)), P<0.001. Chemotherapy induced a significant further increase in serum collagen IV (167 microg l(-1) prechemo vs 206 microg l(-1) postchemo, P=0.001). There were no correlations between baseline collagen IV levels and response to therapy, age, clinical stage or HER2 status. In conclusion, patients with breast cancer have elevated levels of collagen IV compared to healthy women and collagen IV levels increase further during chemotherapy.

Modulation of ER phosphorylation on serine 118 by endocrine therapy: a new surrogate marker for efficacy.

BACKGROUND: Phosphorylation of serine 118 (ser118) has been reported to be involved in the activation of estrogen receptor (ER). In the present study, we evaluated whether endocrine therapy modulated ER phosphorylation on ser118. PATIENTS AND METHODS: We carried out a tissue microarray that included 80 primary breast tumors obtained before the administration of endocrine therapy. A second tissue microarray included 52 tumors obtained after endocrine therapy from the same patients. Immunostainings were carried out for ER, Pser118ER, Her2, insulin growth factor receptor (IGFR), p21-activated kinase 1 (PAK1), pMAPK, bcl2 and progesterone receptor. RESULTS: Pser118ER staining was higher in Her2- (P = 0.06), IGFR- (P = 0.0002) and pMAPK-expressing tumors (P = 0.001). The level of ER phosphorylation was not different according to the occurrence of clinical tumor response (P = 0.16). Pser118ER expression was significantly reduced by endocrine therapy. The mean Pser118ER score was 163 [standard deviation (SD) 81] before endocrine therapy and 80 (SD 90) after endocrine therapy (P = 0.0001, paired t-test). The magnitude of Pser118ER decrease was higher in tumors that responded to endocrine therapy (mean decrease 128, SD 86) as compared with refractory tumors (mean decrease 38, SD 130) (P = 0.017, t-test). CONCLUSION: These findings suggest that endocrine therapy modulates ER on ser118. Pser118ER immunostaining could be used as surrogate marker to monitor treatment efficacy.