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BackgroundThe 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively.MethodsPatients diagnosed with pN0–1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models.ResultsA total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%).ConclusionsOld patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.

Background Trastuzumab has changed the prognosis of HER2+ breast cancer. We aimed to investigate the prognosis of ER+/HER2+ patients treated with trastuzumab, thus to guide escalation endocrine treatment in ER+ breast cancer. Methods ER-positive early breast cancer patients operated at Ruijin Hospital between Jan. 2009 and Dec. 2017 were retrospectively included. Eligible patients were grouped as HER2-negative (HER2-neg) or HER2-positive with trastuzumab treatment (HER2-pos-T). Kaplan-Meier analysis and Cox proportional hazards model were used to compare the disease-free survival (DFS) and overall survival (OS) between these two groups. Results A total of 3761 patients were enrolled: 3313 in the HER2-neg group and 448 in the HER2-pos-T group. Patients in the HER2-pos-T group were associated with pre/peri-menopause, higher histological grade, LVI, higher Ki-67 level, lower ER and PR levels (all P P = 0.185), respectively. Multivariable analysis demonstrated that patients in the HER2-pos-T group had a better DFS than patients in the HER2-neg group (HR 0.52, 95% CI: 0.37–0.73, P P = 0.133). Multivariate analysis found that HER2-pos-T group was still associated with significantly better OS compared with the HER2-neg group (HR 0.38, 95% CI: 0.22–0.67, P = 0.037). Conclusion ER+/HER2+ breast cancer patients treated with trastuzumab were associated with superior outcome compared with ER+/HER2- patients, indicating HER2-positivity itself may not be an adverse factor for ER+ patients in the era of trastuzumab.

Background Toremifene (TOR) is a selective oestrogen receptor modulator (SERM) and has comparable efficacy to that of tamoxifen (TAM) in breast cancer patients. Herein, we compared the safety of TOR to that of TAM in the adjuvant treatment of premenopausal breast cancer. Methods This was a prospective randomized and open-label clinical study. Premenopausal patients with hormonal receptor (HR)-positive early breast cancer were randomly assigned (1:1) to receive TOR) or TAM treatment. The follow-up period was 1 year. The primary end point was the incidence of ovarian cysts, and secondary end points were the incidence of endometrial thickening, changes in female hormones, the incidence of fatty liver, changes in the modified Kupperman index (mKMI) and changes in quality of life. Results There were 92 patients in the final analysis. The incidences of ovarian cysts were 42.6% in the TOR group and 51.1% in the TAM group (p = 0.441). Forty-one patients (87.2%) in the TOR group and 36 patients (80.0%) in the TAM group experienced endometrial thickening (p = 0.348). The proportions of patients with fatty liver were 31.9% in the TOR group and 26.7% in the TAM group (p = 0.581). No significant differences in the mKMI or quality of life were observed between the two groups. Conclusions TOR and TAM have similar side effects on the female genital system and quality of life in premenopausal early breast cancer patients. Trial registration ClinicalTrials.gov NCT02344940. Registered 26 January 2015 (retrospectively registered).

Background To investigate the accuracy of core needle biopsy (CNB) in evaluating breast cancer estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 status and to identify factors which might be associated with Ki67 value change after CNB. Methods A retrospective study was carried out on 276 patients with paired CNB and surgically removed samples (SRS). Clinico-pathological factors as well as the surgery time interval (STI) between CNB and surgery were analyzed to determine whether there were factors associated with Ki67 value change after CNB. Five tumor subtypes were classified as follows: Luminal A, Luminal B-HER2-, Luminal B-HER2+, Triple Negative (TN), and HER2+. Ki67 value change was calculated as SRS minus CNB. Results Mean STI after CNB was 4.5 (1-37) days. Good agreement was achieved for ER, PR, and HER2 evaluation between CNB and SRS. However, Ki67 expression level was significantly higher in SRS compared with CNB samples: 29.1 % vs. 26.2 % (P 7 % Ki67 increase was noticed in patients with STI ≥ 5 days. Conclusion CNB was accurate in evaluating ER, PR, HER2, and molecular subtype status. Ki67 value significantly increased after CNB, which was associated with STI and molecular subtype. Further translational research needs to consider Ki67 changes following CNB among different breast cancer molecular subtypes. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1853-1) contains supplementary material, which is available to authorized users.

Background Sentinel lymph node (SLN) biopsy has been used to assess patients with papillary thyroid carcinoma (PTC). To achieve its full potential the rate of SLN identification must be as close to 100 percent as possible. In the present study we compared the combination of preoperative lymphoscintigraphy scanning by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery, and methylene blue with methylene blue, alone, for sentinel node identification in younger women with unilateral low-risk PTC. Methods From January 2004 to January 2007, 90 female patients, ages 23 to 44 (mean = 35), with unilateral low-risk PTC (T1-2N0M0) were prospectively studied. Mean tumor size was 1.3 cm (range, 0.8-3.7 cm). All patients underwent unilateral modified neck dissection. Prior to surgery, patients had, by random assignment, identification and biopsy of SLNs by methylene blue, alone (Group 1), or by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery and methylene blue (Group 2). Results In the methylene blue group, SLNs were identified in 39 of 45 patients (86.7%). Of the 39 patients, 28 (71.8%) had positive cervical lymph nodes (pN+), and 21 patients (53.8%) had pSLN+. In 7 of the 28 pN+ patients (25%), metastases were also detected in non-SLN, thus giving a false-negative rate (FNR of 38.9% (7/18), a negative predictive value (NPV) of 61.1% (11/18), and an accuracy of 82.1% (32/39). In the combined technique group, the identification rate (IR) of SLN was 100% (45/45). Of the 45 patients, 27 (60.0%) had pN+, 24 (53.3%) had pSLN+. There was a FNR of 14.3% (3/21), a NPV of 85.7% (18/21), and an accuracy of 93.3% (42/45). The combined techniques group was significantly superior to the methylene blue group in IR (p = 0.035). There were no significant differences between two groups in sensitivity, specificity, NPV, or accuracy. Location of pN+ (55 patients) in 84 patients was: level I and V, no patients; level II, 1 patient (1.2%); level III, 6 patients (7.2%); level III and IV, 8 patients (9.5%); level IV, alone, 8 patients (9.5%); level VI, 32 patients (38.1%). In all 90 patients, IR of SLN was 93.3%, FNR, 25.6%, NPV, 74.4%, and accuracy rate, 88.1 percent. Conclusions Compared to a single technique, there was a significantly higher SLN identification rate for the combined technique in younger female with ipsilateral, low-risk PTC (T1-2N0M0). Thus, a combined SLN biopsy technique seems to more accurately stage lymph nodes, with better identification of SLN located out of the central compartment. Regardless of the procedure used, the high FNR renders the current SLN techniques unsuitable for routine practice. Based on these results, prophylactic node dissection of level VI might be considered because 38.1% of our patients had such node metastases.

Background This study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC). Methods One-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67). Results Patients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p < 0.001, p = 0.001, respectively). Conclusion This study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.

Background Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented. Methods Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive. Results There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB. Conclusion CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors.