Pathological complete response, category change, and prognostic significance of HER2-low breast cancer receiving neoadjuvant treatment: a multicenter analysis of 2489 cases.

BACKGROUND: HER2-low breast cancers (BC) show a good response to novel anti-HER2 antibody-drug conjugates (ADCs) in advanced setting. Nevertheless, little is known about the response, category change, and prognosis of HER2-low BC receiving neoadjuvant treatment (NAT). METHODS: Consecutive invasive BC patients who underwent ≥ 4 cycles of NAT and surgery from January 2009 to December 2020 were retrospectively reviewed. HER2-low was defined as IHC 1+ or 2+ and FISH negative. Concordance rates of HER2 and other biomarkers were analyzed by Kappa test. Kaplan-Meier analysis and Cox regression were used to assess the recurrence-free interval (RFI) and overall survival (OS). RESULTS: A total of 2489 patients were included, of whom 1023 (41.1%) had HER2-low tumors. HER2-low patients had a higher ER positivity rate than HER2-0 patients (78.5% vs. 63.6%, P < 0.001), and a similar breast pathological complete response (pCR) rate (20.6% vs. 21.8%, P = 0.617). Among non-pCR cases, 39.5% of HER2-0 tumors changed to HER2-low, and 14.3% of HER2-low tumors changed to HER2-0 after NAT. Low concordance rates of HER2-low status were found in both ER-positive (Kappa = 0.368) and ER-negative (Kappa = 0.444) patients. Primary HER2-low patients had a significantly better RFI than HER2-0 patients (P = 0.014), especially among ER-positive subset (P = 0.016). Moreover, HER2-low category change was associated with RFI in ER-positive subset (adjusted P = 0.043). CONCLUSIONS: Compared with HER2-0 patients, HER2-low patients had a high proportion of ER-positive tumor and a similar pCR rate, which were related with better prognosis, especially in residual cases after NAT. A remarkable instability of HER2-low status was found between the primary and residual tumor, indicating re-testing HER2 status after NAT in the new era of anti-HER2 ADCs therapy.

Efficacy of adjuvant chemotherapy stratified by age and the 21-gene recurrence score in estrogen receptor-positive breast cancer.

BACKGROUND: The 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. METHODS: Patients 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. RESULTS: A 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%). CONCLUSIONS: Old patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.

A prospective, randomized study of Toremifene vs. tamoxifen for the treatment of premenopausal breast cancer: safety and genital symptom analysis.

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).

Clinicopathological Features and Disease Outcome in Breast Cancer Patients with Hormonal Receptor Discordance between Core Needle Biopsy and Following Surgical Sample.

BACKGROUND: There are limited data about how to manage patients with discordant hormonal receptor (HR) status between core needle biopsy (CNB) and following surgical sample (FSS). This study aimed to evaluate clinicopathological features and disease outcome for these HR discordance patients. PATIENTS AND METHODS: Invasive breast cancer patients with paired HR between CNB and FSS were retrospectively analyzed, being classified into three groups: HR positive, HR negative, and HR discordance. Patient characteristics, treatment decisions, and disease outcome were compared among above groups. RESULTS: A total of 1710 patients (1233 HR positive, 417 HR negative, and 60 HR discordance patients) were enrolled. Compared with the HR positive group, HR discordance patients were associated with more human epidermal growth factor receptor 2 positivity (P < 0.001) and higher Ki67 level (P = 0.001) tumors. The fraction of patients receiving adjuvant chemotherapy was 95.0% and 93.8% in the HR discordance or HR negative groups, much higher than in the HR positive group (66.7%, P < 0.001). Of 60 HR discordance patients, 34 (56.7%) received adjuvant endocrine therapy. The 5-year disease-free survival (DFS) rate was 90.4% for HR discordant patients, showing no statistical difference compared with HR positive (87.0%, P = 0.653) or HR negative (83.2%, P = 0.522) groups. For HR discordance patients, there was no difference in DFS between patients who received adjuvant endocrine therapy or not (P = 0.259). CONCLUSIONS: HR discordance patients had similar tumor characteristics, adjuvant chemotherapy treatment, and DFS compared with HR negative patients. The benefit of endocrine therapy in these HR discordance patients is uncertain and deserves further clinical evaluation.

Surgery time interval and molecular subtype may influence Ki67 change after core needle biopsy in breast cancer patients.

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 < 0.001). Both univariate and multivariate analysis demonstrated that STI and molecular subtype were associated with a Ki67 change after CNB. Luminal A tumors experienced more Ki67 elevation than Luminal B-HER2- diseases (6.2 % vs -0.1 %, P = 0.014). Patients with longer STI after CNB had a higher Ki67 increase: -1.1 % within 1-2 days, 2.1 % with 3-4 days, and 5.6 % more than 4 days, respectively (P = 0.007). For TN and HER2+ tumors, the Ki67 change was apt to be 0 with STI ≤ 4 days, while a >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.

Preoperative core needle biopsy is accurate in determining molecular subtypes in invasive breast cancer.

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.

Tumor size is associated with adjuvant chemotherapy benefit in T1N0M0 triple-negative breast cancer: a multicenter and propensity score matched analysis.

Background: Triple-negative breast cancer (TNBC) is characterized by aggressive phonotypes and relatively poor outcomes. There are controversies on the effect of adjuvant chemotherapy in small (T1N0M0) TNBCs, especially among T1a-b patients. This study evaluated the survival benefit of adjuvant chemotherapy and influential factors in T1N0M0 TNBC patients. Methods: All T1N0M0 TNBC patients were identified from the Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB) between January 2009 and December 2021. Propensity score matched (PSM) was applied to create a matched cohort. We used Kaplan-Meier analysis and Cox regression models to evaluate the associations of adjuvant chemotherapy with breast cancer-free interval (BCFI) and overall survival (OS). Stratified analysis according to different influential factors was also performed. Results: In total, 1,113 T1N0M0 TNBC patients (297 T1a, T1b and 816 T1c) were enrolled, including 928 patients with adjuvant chemotherapy and 185 patients without adjuvant chemotherapy. After matching 441 patients by using PSM analysis, 294 patients with chemotherapy and 147 patients without chemotherapy were identified. Patients with or without chemotherapy had similar BCFI (P=0.241) and OS (P=0.509). However, regarding patients with different tumor sizes, adjuvant chemotherapy could significantly improve BCFI in T1c patients (5-year BCFI: 92.1% vs. 79.5%, P=0.035) but not in T1a-b patients (5-year BCFI: 93.6% vs. 94.6%, P=0.546). No significant difference in OS was observed among patients with different tumor sizes. Subgroup analysis found that only tumor size was significantly associated with adjuvant chemotherapy benefit in terms of BCFI (Pinteraction=0.021) and OS (Pinteraction=0.040). Conclusions: The survival benefit of adjuvant chemotherapy was significantly associated with tumor size in T1N0M0 TNBC. Benefit of adjuvant chemotherapy was found in T1c, but not in T1a-b patients. Our findings do not support the routine use of chemotherapy in patients with T1a-bN0 TNBC.

Time interval between breast cancer diagnosis and surgery is associated with disease outcome.

Time interval between breast cancer (BC) diagnosis and surgery is of concern to patients and clinicians, but its impact on survival remains unclear. We identified 5130 BC patients receiving surgery between 2009 and 2017 from the Shanghai Jiaotong University Breast Cancer Database (SJTU-BCDB), and divided as Ruijin cohort and SJTU cohort. All participants were divided into three groups according to the interval between diagnosis and surgery: ≤ 1 week, 1-2 weeks, and > 2 weeks. Among 3144 patients of Ruijin cohort, the estimated 5-year breast cancer-free interval (BCFI) rates for the ≤ 1 week, 1-2 weeks and > 2 weeks groups were 91.8%, 87.5%, and 84.0% (P = 0.088), and the estimated 5-year overall survival (OS) rates were 95.6%, 89.6%, and 91.5% (P = 0.002). Multivariate analysis showed that patients with a TTS > 2 weeks had significantly lower BCFI (HR = 1.80, 95%CI 1.05-3.11, P = 0.034) and OS (HR = 2.07, 95% CI 1.04-4.13, P = 0.038) rates than patients with a TTS ≤ 1 week. Among 5130 patients when combining Ruijin cohort with SJTU cohort, the estimated 5-year BCFI rates for the ≤ 1 week, 1-2 weeks, and > 2 weeks groups were 91.0%, 87.9%, and 78.9%, and the estimated 5-year OS rates for the ≤ 1 week, 1-2 weeks, and > 2 weeks groups were 95.8%, 90.6%, and 91.5%, both with a significantly p value < 0.001. Our findings demonstrated the prolonged time to surgery (more than 2 weeks) after BC diagnosis was associated with poor disease outcomes, suggesting that efforts to early initiate treatment after diagnosis need to be pursued where possible to improve survival.

Experimental Study on Shear-Peeling Debonding Behavior of BFRP Sheet-to-Steel Interfaces.

In order to study the failure mode and debonding behavior of the interface between BFRP (basalt fiber reinforced polymer) sheet and structural steel under mixed-mode loading conditions, eighteen specimens with different initial angles were tested in this study. The specimens were designed with different initial angles to ensure that the interface performed under mixed-mode loading conditions. The relations between the bond strengths, failure modes, and initial angles were investigated. A new evaluation method to predict the interfacial bond strength under shear-peeling loading mode was proposed. The test results show that specimens with a smaller initial angle are more likely to exhibit a shear debonding failure at the interface between the steel plate and adhesive. In contrast, specimens with a larger initial angle are more likely to exhibit peeling of the interface. The ultimate tensile strength of the specimen is higher with a smaller initial angle. The results predicted by the proposed method are in good agreement with the experimental results.

Primary breast osteosarcoma in a patient previously treated for ipsilateral invasive ductal carcinoma: An unusual case report with clinical and genomic features.

Primary breast osteosarcoma is a rare subtype of breast malignancy with limited clinical evidence, inadequate biological understanding, and unmet treatment consensus. Here, we report an unusual case of primary breast osteosarcoma developing in the same quadrant of the breast 2 years after initial dissection and radiation of invasive ductal carcinoma. Thorough evaluations of imaging and pathology were conducted while genomic alterations of both primary and secondary tumors, as well as peripheral blood samples, were explored through the next-generation sequencing technique. A comprehensive review of the current literature was also performed on this rare malignancy.

HER2-Low Status Is Not Accurate in Breast Cancer Core Needle Biopsy Samples: An Analysis of 5610 Consecutive Patients.

Background: HER2-Low status is found in approximately half of breast cancer patients and shows potential benefits from novel antibody−drug conjugates (ADCs). Data on the accuracy of HER2-Low status between core needle biopsy (CNB) and surgical excision specimen (SES) samples are lacking. We aimed to investigate the accuracy of HER2-Low status diagnosis between CNB and SES samples. Methods: Consecutive early-stage breast cancer patients who underwent surgery from January 2009 to March 2022 with paired CNB and SES samples were retrospectively reviewed. HER2-Low was defined as IHC 1+ or IHC2+ and FISH-negative. Concordance rates were analyzed by the Kappa test. Further clinicopathological characteristics were compared among different HER2 status and their changes. Results: A total of 5610 patients were included, of whom 3209 (57.2%) and 3320 (59.2%) had HER2-Low status in CNB and SES samples, respectively. The concordance rate of HER2 status in the whole population was 82.37% (Kappa = 0.684, p < 0.001), and was 76.87% in the HER2-Negative patients (Kappa = 0.372, p < 0.001). Among 1066 HER2-0 cases by CNB, 530 patients were classified as HER2-Low tumors. On the contrary, in 3209 patients with HER2-Low tumor by CNB, 387 were scored as HER2-0 on the SES samples. ER-negative or Ki67 high expression tumor by CNB had a high concordance rate of HER2-Low status. Conclusions: A relatively low concordance rate was found when evaluating HER2-Low status between CNB and SES samples in HER2-Negative breast cancer patients, indicating the necessity of retesting HER2 low status at surgery, which may guide further therapy in the era of anti-HER2 ADCs.

The Comparative Safety of Epirubicin and Cyclophosphamide versus Docetaxel and Cyclophosphamide in Lymph Node-Negative, HR-Positive, HER2-Negative Breast Cancer (ELEGANT): A Randomized Trial.

Background: In adjuvant settings, epirubicin and cyclophosphamide (EC) and docetaxel and cyclophosphamide (TC) are both optional chemotherapy regimens for lymph node-negative, hormone receptor (HR)-positive, human epidermal receptor 2 (HER2)-negative breast cancer patients. Neutropenia is one of the most common adverse events (AEs) of these regimens. The rate of grade 3−4 neutropenia varies in different studies, and direct comparisons of safety profiles between EC and TC are lacking. Method: ELEGANT (NCT02549677) is a prospective, randomized, open-label, noninferior hematological safety trial. Eligible patients with lymph node-negative HR+/HER2-tumors (1:1) were randomly assigned to received four cycles of EC (90/600 mg/m2) or TC (75/600 mg/m2) every three weeks as adjuvant chemotherapy. The primary endpoint was the incidence of grade 3 or 4 neutropenia defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 on an intention-to-treat basis. Noninferiority was defined as an upper 95% CI less than a noninferiority margin of 15%. Results: In the intention-to-treat population, 140 and 135 patients were randomized into the EC and TC arms, respectively. For the primary endpoint, the rate of grade 3 or 4 neutropenia is 50.71% (95% CI: 42.18%, 59.21%) in the EC arm and 48.15% (95% CI: 39.53%, 56.87%) in the TC arm (95%CI risk difference: −0.100, 0.151), showing the noninferiority of the EC arm. For secondary endpoints, the rate of all-grade anemia is higher in the EC arm (EC 42.86% versus TC 22.96%, p = 0.0007), and more patients suffer from nausea/vomiting, hair loss, and nail changes (p < 0.01) in the EC arm. No statistically different disease-free survival was observed between the two arms (p = 0.13). Conclusion: EC is not inferior to TC in the rate of grade 3 or 4 neutropenia, but more other AEs were observed in the EC group.

Molecular Subtype May Be More Associated With Prognosis and Chemotherapy Benefit Than Tumor Size in T1N0 Breast Cancer Patients: An Analysis of 2,168 Patients for Possible De-Escalation Treatment.

PURPOSE: Breast cancer (BC) patients with T1N0 tumors have relatively favorable clinical outcomes. However, it remains unclear whether molecular subtypes can aide in prognostic prediction for such small, nodal-negative BC cases and guide decision-making about escalating or de-escalating treatments. PATIENTS AND METHODS: T1N0 BC patients diagnosed between 2009 and 2017 were included and classified into three subgroups according to receptor status: 1) hormonal receptor (HR)+/human epidermal growth factor receptor-2 (HER2)-; 2) HER2+; and 3) triple negative (TN) (HR-/HER2-). Patients' characteristics and relapse events were reviewed. Kaplan-Meier analysis and Cox regression were used to assess the iDFS and BCSS. The effects of risk factors and adjuvant treatment benefits were evaluated by calculating hazard ratios (HRs) for invasive disease-free survival (iDFS) and breast cancer-specific survival (BCSS) with Cox proportional hazards models. RESULTS: In total, 2,168 patients (1,435 HR+/HER2-, 427 HER2+, 306 TN) were enrolled. The 5-year iDFS rates were 93.6, 92.7, and 90.6% for HR+/HER2-, HER2+, and TN patients, respectively (P = 0.039). Multivariate analysis demonstrated that molecular subtype (P = 0.043), but not tumor size (P = 0.805), was independently associated with iDFS in T1N0 BC. TN patients [HRs = 1.77, 95% confidence interval (CI) = 1.11-2.84, P = 0.018] had a higher recurrence risk than HR+/HER2- patients. Adjuvant chemotherapy benefit was not demonstrated in all T1N0 patients but interacted with molecular subtype status. TN (adjusted HRs = 2.31, 95% CI = 0.68-7.54) and HER2+ (adjusted HRs = 2.26, 95% CI = 0.95-5.63) patients receiving chemotherapy had superior iDFS rates. Regarding BCSS, molecular subtype tended to be related to outcome (P = 0.053) and associated with chemotherapy benefit (P = 0.005). CONCLUSION: Molecular subtype was more associated with disease outcome and chemotherapy benefit than tumor size in T1N0 BC patients, indicating that it may guide possible clinical de-escalating therapy in T1N0 BC.

Comprehensive Association Analysis of 21-Gene Recurrence Score and Obesity in Chinese Breast Cancer Patients.

PURPOSE: A center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients. PATIENTS AND METHODS: Luminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status. RESULTS: Among 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P<0.05). Compared to non-overweight patients, obese ones presented significantly higher ER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all P<0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population. CONCLUSIONS: RS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.

Prognostic value of the 21-gene recurrence score in ER-positive, HER2-negative, node-positive breast cancer was similar in node-negative diseases: a single-center study of 800 patients.

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Among 800 patients recruited between 2009 and 2016, the median RS was 24 (0-69), with 27.4%, 46.8%, and 25.9% patients classified into low-, intermediate-, and high-risk groups. Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) events compared with the low-risk category (IDFS: HR = 2.450, 95% CI 1.017-5.902, P = 0.046; DDFS: HR = 2.829, 95% CI 1.013-7.901, P = 0.047). No significant association between RS category and overall survival (OS) was found (intermediate vs. low: HR= 1.244, 95% CI 0.292-5.297, P = 0.768; high vs. low: HR = 2.933, 95% CI 0.759-11.327, P = 0.119). RS, as a continuous variable, was a highly significant predictor for IDFS (HR= 1.028, 95% CI 1.010-1.047, P = 0.002), DDFS (HR= 1.030, 95% CI 1.010-1.051, P = 0.003), and OS (HR= 1.034, 95% CI 1.007-1.063, P = 0.014). Our findings suggested that RS may predict IDFS in Chinese patients with ER+/HER2- breast cancer with N0 or N1 disease.

Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study.

PURPOSE: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). MATERIALS AND METHODS: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. RESULTS: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). CONCLUSION: RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

A high absolute lymphocyte count predicts a poor prognosis in HER-2- positive breast cancer patients treated with trastuzumab.

Background: Immune responses play an important role in the development of breast cancer. Trastuzumab can activate antibody-dependent cellular cytotoxicity (ADCC) in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. Many studies have demonstrated that inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC), are associated with prognosis in breast cancer. The aim of this study was to explore whether preoperative NLR, ALC or the absolute neutrophil count (ANC) is associated with prognosis in HER-2-positive breast cancer patients who received adjuvant trastuzumab. Patients and methods: Three hundred sixty-seven female patients with HER-2-positive invasive breast cancer who were treated with one-year adjuvant trastuzumab were analysed in this retrospective study. Preoperative haematological parameters, clinicopathological data and survival data were obtained. The cut-off points for ALC, ANC and NLR were based on the median values. Disease-free survival (DFS) and Overall survival (OS) were analysed by the Kaplan-Meier method. Multivariable Cox regression was used to determine the independent prognostic significance of ALC, ANC and NLR. Results: Survival analysis revealed that the 3-year DFS in patients with high ALC was 89.0%, which was significantly worse than 95.0% in patients with low ALC (p=0.014). Kaplan-Meier analysis also showed that patients with low NLR had a poorer 3-year DFS than patients with high NLR (89.7% vs 94.0%, respectively; p=0.047). Multivariate analysis showed that ALC was an independent prognostic factor for DFS (HR=2.723; 95% CI=1.211-6.122; p=0.015). Neither ANC, ALC nor NLR could predict OS independently. Conclusion: In HER-2-positive breast cancer patients who were treated with adjuvant trastuzumab, a high ALC is significantly associated with a poor DFS.

21-Gene recurrence score influences the chemotherapy decision for patients with breast cancer of different luminal subtypes.

Luminal subtypes and the 21-gene recurrence score (RS) are important factors in the decision-making process for adjuvant chemotherapy in patients with hormonal receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, their effect on adjuvant chemotherapy decisions in the real world has not been thoroughly investigated, particularly for patients of the luminal A-like subtype with a high RS or the luminal B-like subtype with a low RS. The present study, a total of 772 HR+/HER2- patients who underwent 21-gene testing, were included in a retrospective analysis. The impact of clinicopathological factors and the 21-gene RS on chemotherapy recommendation was analyzed in the whole population and for patients of different luminal subgroups. The results revealed that chemotherapy was highly recommended for patients of younger age, with larger tumor size, node involvement, higher grade, luminal B-like subtype and higher RS. A high RS was identified to be the most important impact factor for chemotherapy recommendation among all patients [odds ratio (OR), 62.54; 95% CI, 25.58-152.92], the luminal A-like group (OR, 435.05; 95% CI, 29.90-6331.06) and the luminal B-like group (OR, 57.20; 95% CI, 22.42-145.96). For patients of the luminal A-like subtype with a high RS or patients of the luminal B-like subtype with low RS, the 21-gene RS was demonstrated to be the most important independent factor for chemotherapy recommendation, with an adjusted OR of 134.52 (95% CI, 10.39-1741.89). In conclusion, luminal subtypes and the 21-gene RS were found to be associated with chemotherapy recommendation for HR+/HER2- patients. For patients with a discordant luminal subtype and 21-gene RS risk, the 21-gene RS score was found to be the most important factor that influences chemotherapy decision, which warrants further clinical evaluation.

Distribution and Clinical Utility of the 21-gene Recurrence Score in Pure Mucinous Breast Cancer Patients: a case-control study.

The 21-gene recurrence score (RS) is increasingly being used for patients with early stage, hormone receptor-positive, Her-2-negative breast cancer. However, these results are largely from populations with infiltrating ductal carcinoma (IDC). The clinical value of RS testing in mucinous carcinoma has not been well investigated. Pure mucinous breast cancer (PMBC) and paired pure IDC patients who underwent 21-gene RS were retrospectively reviewed and matched with tumor stage and molecular subtype. Clinic-pathological factors, treatment strategies, and RS distribution were compared between the PMBC and IDC patients. A total of 35 PMBC and 70 IDC patients were included. We found that RS was lower in the PMBC as compared with the IDC group: 21.26 vs. 24.40 (P=0.037). Regarding RS categories, PMBC patients had a relatively lower percentage of high RS patients than the IDC group: 8.57% vs. 22.86% (P = 0.048). Multivariate analysis showed that histologic type was an independent factor predicting RS distribution: IDC patients were associated with a higher RS as compared with PMBC patients (OR: 1.27, 95% CI: 1.03-2.13; P=0.014). Among genes in 21-gene RS testing, HER2, STMY3, STK15, and BAG1 were significantly different between the PMBC and IDC groups (P < 0.05). Two patients (5.71%) in the PMBC group, both with high RS, were recommended to receive adjuvant chemotherapy, much lower than patients with IDC (57.14%, P < 0.001). In multivariate analysis, histologic type of IDC was an independent factor for chemotherapy recommendation (OR = 22.00, 95% CI: 4.89-98.97, P<0.001). With a medium follow-up time of 24 months, one IDC patient had ipsilateral axillary lymph nodes recurrence and one PMBC patient had contralateral breast cancer. In conclusion, PMBC patients, mostly classified with low or intermediate RS category, were associated with lower RS as compared with IDC patients. PMBC and IDC had different genes expression patterns. Patients with high RS in the PMBC group might be recommended to receive adjuvant chemotherapy, which deserves further clinical evaluation.