Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

Monitoring trends in the absolute lymphocyte count and the neutrophil-to-lymphocyte ratio in patients with breast cancer receiving eribulin.

BACKGROUND: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes. METHODS: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival. RESULTS: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals. CONCLUSION: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.

Quality of care in the course of subcutaneous versus intravenous trastuzumab administration in patients with breast cancer: an integrated time-motion study with mixed-methods research.

OBJECTIVES: This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC). DESIGN: This observational time-motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses. SETTING: Outpatient and inpatient administration units of a single medical centre in Taiwan. PARTICIPANTS: The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses. RESULT: Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak. CONCLUSION: Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic.

Does the Timing of Eribulin Treatment for Advanced or Metastatic Breast Cancer Matter? Evidence from a Real-World Setting.

BACKGROUND: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients. METHODS: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed. RESULTS: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%). CONCLUSIONS: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.

Contribution of Interleukin-10 Genotype to Triple Negative Breast Cancer Risk.

BACKGROUND/AIM: Triple negative breast cancer (TNBC) is characterized by increased recurrence and poor survival. Mounting evidence suggests that interleukin-10 (IL-10) plays a role in carcinogenesis, however, little is known about the contribution of IL-10 to TNBC. The study evaluated the contribution of IL-10 promoter A-1082G (rs1800896), T-819C (rs3021097), A-592C (rs1800872) genotypes to the risk of TNBC. MATERIALS AND METHODS: IL-10 genotypes were examined among 1,232 breast cancer patients and 1,232 controls and evaluated. RESULTS: The percentages of AG and GG for IL-10 A-1082G genotypes were higher in the breast cancer patient group than in the control group. The GG genotype carriers were of higher risk for breast cancer [odds ratio (OR)=2.02, 95% confidence interval (CI)=1.28-3.21, p=0.0021]. Interestingly, G allele carriers were of higher risk of TNBC (OR=1.25, 95%CI=1.07-1.46, p=0.0050). CONCLUSION: The G allele of IL-10 A-1082G genotype may serve as a predictor for TNBC risk. The finding should be validated in other populations.

Interleukin-13 Promoter Genotypes and Taiwanese Breast Cancer Susceptibility.

BACKGROUND/AIM: The current study aimed at evaluating the contribution of IL-13 promoter rs1881457 and rs1800925 genotypes to the risk of breast cancer in Taiwan. MATERIALS AND METHODS: A total of 1,232 breast cancer cases and 1,232 age-matched controls were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: As for IL-13 rs1881457, the rates of AA, AC and CC genotypes were 54.8, 37.9 and 7.3% among the cases, and 53.8, 38.7 and 7.5% among the healthy controls, respectively; there were no statistically significant differences between the two groups (p for trend=0.8889). Also, regarding IL-13 rs1800925, there were no statistically significant differences between the two groups either (p for trend=0.6803). Furthermore, the allelic frequencies for IL-13 rs1881457 and rs1800925 were not differentially distributed between the case and control groups (p=0.6515 and 0.8753, respectively). CONCLUSION: The rs1881457 and rs1800925 IL-13 promoter polymorphisms may not serve as breast cancer susceptibility determinants for Taiwanese.

Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk.

Compared with other subgroups of breast cancer, triple negative breast cancer (TNBC) is considered to be the one with the greatest invasiveness and metastatic mobility, and the highest recurrence rate. Considering the lack of predictive markers for TNBC, we aimed to examine the contribution of excision repair cross complementing-group 1 (ERCC1) genotypes to TNBC. The rs11615 and rs3212986 of ERCC1 were investigated and evaluated for their associations with susceptibility to breast cancer, especially TNBC, in Taiwan. In this study, 1,232 breast cancer patients (104 were TNBC) and 1,232 healthy controls were recruited and their genotypes at ERCC1 rs11615 and rs3212986 were revealed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Our results indicated that genotypes of ERCC1 rs11615 (Ptrend = 2.2*10E-9), but not rs3212986 (Ptrend = 0.6181), were associated with breast cancer risk. In the allelic frequency distribution analysis, breast cancer patients carried the T allele of ERCC1 rs11615 a higher rate than the control subjects, further supporting the idea that ERCC1 rs11615 TT genotype is positively associated with breast cancer susceptibility. More importantly, the frequency of the ERCC1 rs11615 TT genotype was even higher among TNBC patients than among other subtypes of breast cancer patients (P = 0.0001, odds ratio = 1.73, 95% confidence interval = 1.15-2.63). The genotypes of ERCC1 rs11615 were not associated with Ki67 status. Our findings firstly show that the T allele of ERCC1 rs11615 can serve as a predictive biomarker for breast cancer and TNBC. We believe that ERCC1 could serve as a target for personalized treatment of breast cancer, especially for TNBC.

The Association of Matrix Metalloproteinase-1 Promoter Polymorphisms with Breast Cancer.

BACKGROUND/AIM: The family of matrix metalloproteinases (MMPs) are responsible for the homeostasis of extracellular matrix components and their genetic polymorphisms may be associated with cancer susceptibility. The serum levels of MMP-1 have been reported to be lower in breast cancer patients than healthy subjects. In the current study, we aimed at investigating the contribution of a polymorphism in the promoter region of MMP-1 to breast cancer in Taiwan. MATERIALS AND METHODS: The MMP-1 rs1799705 polymorphic genotypes were genotyped among 1,232 breast cancer patients and 1,232 healthy controls by the typical polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The percentages of 2G/2G, 1G/2G, and 1G/1G for MMP1 -1607 genotypes were 35.4, 40.6 and 24.0% in the breast cancer group and 34.1, 43.6, and 22.3% in the healthy control group (p trend=0.3025), respectively. The odds ratios (ORs) after adjusting for age, smoking and alcohol drinking status for those carrying 1G/2G and 1G/1G genotypes at MMP1 -1607 were 0.93 (95%CI=0.76-1.11, p=0.2390) and 1.01 (95%CI=0.77-1.23, p=0.7377), respectively, compared to those carrying the wild-type 2G/2G genotype. Supporting this finding, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 1.03 (95%CI=0.91-1.18, p=0.8860), compared to those carrying the wild-type 2G allele. Our findings suggest that the polymorphic genotypes at MMP1 promoter -1607 investigated in the current study, may not play a major role in determining cancer susceptibility to breast cancer in Taiwan. Other early diagnostic and predictive markers are urgently needed for personalized and precise breast cancer detection and therapy.

The Association of Matrix Metalloproteinase-8 Promoter Genotypes in Breast Cancer.

BACKGROUND/AIM: The family of matrix metalloproteinases (MMPs) controls homeostasis of the extracellular matrix and their genetic polymorphisms may be associated with personal cancer susceptibility. The serum levels of MMP8 was reported to be higher in patients with breast cancer than in healthy individuals. In this study, we aimed to investigate the contribution of a polymorphism in the promoter region of MMP8 (-799C/T) and two nonsynonymous polymorphisms (Val436Ala and Lys460Thr) to breast cancer. MATERIALS AND METHODS: MMP8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes were determined for 1,232 patients with breast cancer and 1,232 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The odds ratios (ORs) after adjusting for age, gender, smoking and alcohol drinking status for those carrying CT and TT genotypes at the MMP8 promoter C-799T were 1.03 (95% CI=0.88-1.23, p=0.7475) and 1.08 (95% CI=0.91-1.53, p=0.3561), respectively, compared to those carrying the wild-type CC genotype. The OR for the combined T-bearing genotypes were of a similar non-significant level (OR=1.05, 95% CI=0.90-1.26, p=0.5176). Supporting this finding, the adjusted OR for those carrying the T allele at MMP8 C-799T was 1.05 (95% CI=0.86-1.21, p=0.3797), compared to those carrying the wild-type C allele. There was also no significant association of MMP8 Lys460Thr with breast cancer. There was no polymorphic genotype at MMP8 Val436Ala found among any of the investigated individuals. CONCLUSION: MMP8 -799C/T, Val436Ala and Lys460Thr polymorphisms may only play an indirect role in determining personal cancer susceptibility to breast cancer in Taiwan.

Efficacy and toxicity of pegylated liposomal doxorubicin-based chemotherapy in early-stage breast cancer: a multicenter retrospective case-control study.

AIM: PEGylated liposomal doxorubicin (PLD) has comparable efficacy and differing toxicity from conventional anthracyclines used to treat advanced breast cancer. This study compared disease-free survival and toxicity between PLD-based and conventional anthracycline-based regimens as adjuvant treatments for early-stage breast cancer. METHODS: We analyzed disease-free survival (DFS) rates, and adverse events in 102 women with early-stage (I-IIIa) breast cancer who received adjuvant PLD-based chemotherapy from 2002 to 2008. Each patient was matched for age, stage at diagnosis, HER-2 expression and hormone therapy use to a patient treated with an epirubicin-based regimen. Fisher's exact and Pearson's chi-square tests were used for categorical data analysis. Kaplan-Meier analysis and Cox regression models were used to analyze DFS. RESULTS: DFS at 5 years was 81.3% for PLD-based regimen and 82.3% for epirubicin-based regimen. This difference was not significant (p = 0.939). Stage IIIa disease was associated with a shorter DFS in univariate analysis (p = 0.048). In multivariate analysis that controlled for adjuvant treatment, age at diagnosis, stage, HER-2 expression, type of surgery and hormone and radiation therapy, stage IIIa disease (P = 0.023) and lack of hormone therapy (P = 0.024) were each independently associated with shorter DFS. Adverse events were evaluated, and with the exception of hand-foot syndrome, more grade 3 and 4 toxicities occurred in patients who received epirubicin-based regimens than in those given PLD-based regimens. CONCLUSION: For patients with early-stage breast cancer who received PLD-based adjuvant chemotherapy, 5-year DFS was comparable and toxicity was acceptable, yet different from those of patients who received epirubicin-based regimens.

The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes in Breast Cancer in Taiwan.

BACKGROUND/AIM: The matrix metalloproteinase (MMP) family of enzymes are in charge of degradation of various components of the extracellular matrix and their functional genetic polymorphisms may be associated with cancer susceptibility. The functional polymorphisms in the promoter region of MMP7 (A-181G and C-153T) have been reported to influence the binding capacity of nuclear proteins and may contribute to genetic susceptibility to cancer. In this study, we focused on investigating the contribution of the genotypes of MMP7 (A-181G and C-153T) to breast cancer in Taiwan. MATERIALS AND METHODS: These two polymorphisms were genotyped in 1,232 patients with breast cancer and 1,232 controls by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The odds ratios (ORs) after adjusting for age, family history of cancer, smoking and alcohol drinking status for those carrying AG and GG genotypes at MMP7 promoter A-181G were 1.22 (95%CI=0.91-1.63, p=0.2235) and 2.84 (95%CI=1.64-7.48, p=0.0007) respectively, compared to those carrying the wild-type AA genotype. Supporting this finding, the adjusted OR for those carrying the G allele at MMP7 promoter A-181G was 1.57 (95%CI=1.29-1.93, p=0.0008), compared to those carrying the wild-type A allele. There was no polymorphic genotype at MMP7 C-153T found among any of the investigated individuals. CONCLUSION: Our findings suggest that the MMP7 A-181G polymorphisms may play a role in determining personal cancer susceptibility and GG genotype at MMP7 A-181G may serve as a biomarker for early detection and prediction of breast cancer in Taiwanese.

Pegylated Liposomal Doxorubicin as Adjuvant Therapy for Stage I-III Operable Breast Cancer.

BACKGROUND: Conventional anthracyclines play an essential role for the treatment of breast cancer and have potent cytotoxic activity, but are associated with severe toxicity. In metastatic breast cancer, pegylated liposomal doxorubicin (PLD) is a formulation with efficacy similar to conventional doxorubicin but with reduced toxicity. This multicenter study evaluated the efficacy and safety of PLD-based adjuvant chemotherapy for women with stage I-III operable breast cancer. PATIENTS AND METHODS: One hundred and eighty women with stage I-III breast cancer who received PLD-based adjuvant chemotherapy at six different Institutions in Taiwan from February 2002 to March 2008 were included and followed-up until April 2015. Treatment efficacy was determined by disease-free survival (DFS) rate and safety was evaluated by adverse events. RESULTS: The 5- and 10-year DFS rates were 76.3 and 72.6%, respectively. Univariate analysis revealed that tumor size >5 cm (p=0.045; hazard ratio=3.31) and stage III (hazard ratio=3.54; p=0.019) were each associated with shorter DFS. Only stage III (hazard ratio=5.60; p=0.018) retained statistical significance with regard to DFS in the multivariate analysis. Grade 3/4 hematological toxicity was neutropenia (n=13; 7.2%). The women receiving PLD had low-grade 3 or 4 nausea/vomiting, mucositis, and alopecia. Grade 3 hand-foot syndrome occurred in three patients (1.7%). CONCLUSION: PLD could be considered an effective and safe alternative to conventional anthracyclines in the treatment of stage I-III operable breast cancer.

The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk.

The tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins which have been shown to be upregulated in various types of cancers. However, the contribution of TIMPs in breast cancer is not fully understood, not to mention triple negative breast cancer (TNBC). This study's aim was to evaluate the contribution of TIMP-1 rs4898, rs6609533, and rs2070584 genotypes to the risk of breast cancer, especially the subtype of TNBC. The contributions of these TIMP-1 genotypes to cancer risk were examined among 1232 breast cancer patients and 1232 healthy controls, and several clinicopathologic factors were also analyzed. The results showed that the percentages of CC, CT, and TT of TIMP-1 rs4898 were differentially distributed at 28.5%, 33.1% and 38.4% in the breast cancer patient group and 34.5%, 41.0% and 24.5% in the control group, respectively (P for trend = 7.99*10(-13)). It was also found that the CC genotype carriers were of increased risk for breast cancer (odds ratio = 1.90, 95% confidence interval = 1.55-2.33, P = 0.0001) than the TT genotype carriers. In addition, we analyzed the allelic frequency distributions of all three TIMP-1s, and the results showed that the C allele of TIMP-1 rs4898 contributes to an increase in breast cancer susceptibility (P = 2.41*10(-12)). On the other hand, there was no difference found in the distribution of genotypic or allelic frequencies among the patients and the controls for TIMP-1 rs6609533 and rs2070584. Thus, it is our conclusion that the CC genotype of TIMP-1 rs4898 compared to the TT wild-type genotype may increase the risk for breast cancer, especially TNBC in Taiwan, and may serve as an early detective and predictive marker.

Phase 3, open-label, randomized study comparing 3-monthly with monthly goserelin in pre-menopausal women with estrogen receptor-positive advanced breast cancer.

BACKGROUND: Monthly goserelin 3.6 mg dosing suppresses estradiol (E2) production and has proven efficacy in pre-menopausal women with estrogen receptor (ER)-positive breast cancer. This non-inferiority study evaluated the efficacy and safety of 3-monthly goserelin 10.8 mg compared with monthly goserelin 3.6 mg. METHODS: This was a Phase 3, open-label, multicenter trial. Pre-menopausal women with ER-positive advanced breast cancer were randomized to 3-monthly goserelin 10.8 mg or monthly goserelin 3.6 mg; all patients received concomitant tamoxifen (20 mg daily). The primary endpoint was progression-free survival (PFS) rate at 24 weeks; non-inferiority was to be confirmed if the entire 95 % confidence interval (CI) for the treatment difference was above -17.5 %. Secondary endpoints included objective response rate (ORR), serum E2 levels, safety, and tolerability. RESULTS: In total, 222 patients were randomized (goserelin 10.8 mg, n = 109; goserelin 3.6 mg, n = 113). PFS rate at week 24 was 61.5 % (goserelin 10.8 mg) and 60.2 % (goserelin 3.6 mg); treatment difference (95 % CI) was 1.3 % (-11.4, 13.9), confirming non-inferiority of goserelin 10.8 mg compared with goserelin 3.6 mg. ORR was 23.9 % (goserelin 10.8 mg) and 26.9 % (goserelin 3.6 mg); treatment difference (95 % CI) was -3.0 % (-15.5, 9.7). At week 24, mean serum E2 concentrations were similar in the goserelin 10.8 mg and goserelin 3.6 mg groups (20.3 pg/mL and 24.8 pg/mL, respectively). CONCLUSION: A regimen of 3-monthly goserelin 10.8 mg demonstrated non-inferiority compared with monthly goserelin 3.6 mg for PFS rate at 24 weeks, with similar pharmacodynamic and safety profiles, in pre-menopausal women with ER-positive breast cancer.

Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer.

BACKGROUND/AIM: Pegylated liposomal doxorubicin (PLD) has been proven to be an effective antitumor drug for metastatic breast cancer, with less toxicity than conventional anthracycline. Our objective was to evaluate the efficacy and safety of PLD-based adjuvant chemotherapy compared to conventional chemotherapy for patients with stages I-III Triple-negative breast cancer (TNBC). PATIENTS AND METHODS: A total of 162 patients, histologically proven to have TNBC at stages I-III between 2003 and 2010, were enrolled to evaluate the impact of PLD- and non-PLD-based adjuvant chemotherapy by using the end-pint of overall survival (OS) and relapse-free survival (RFS). RESULTS: Forty-nine (30.2%) patients received PLD-based adjuvant chemotherapy and 113 (69.8%) a non-PLD regimen, including 84 (52%) patients receiving non-PLD anthracycline. The Kaplan-Meier calculation indicated no differences in RFS and OS between the PLD and non-PLD groups. Multivariate analysis adjusted for tumor size and lymph node status also revealed similar RFS (HR=0.86, 95% CI=0.43-1.73, p=0.678) and OS (HR=0.86, 95% CI=0.41-1.79, p=0.692) for PLD-based chemotherapy compared with non-PLD-based. Patients receiving PLD-based chemotherapy had a relatively lower incidence of grade 3-4 neutropenia (25% vs. 41.6%, respectively; p=0.054) and significantly higher incidence of hand-foot syndrome (16.3% vs. 4.4%, respectively; p=0.010). CONCLUSION: PLD-based adjuvant chemotherapy was as effective as conventional chemotherapy for patients with TNBC. PLD is an alternative for patients with TNBC when conventional anthracycline is inappropriate.

Contribution of personalized Cyclin D1 genotype to triple negative breast cancer risk.

Aim: Cell cycle regulator cyclin D1 (CCND1) is a pivotal regulator for G1/S phase transition, playing a critical part in initiation of carcinogenesis. Triple negative breast cancer comprises a very heterogeneous group of cancer cells, but little is known about what is wrong in the genome of these patients. This study investigated contribution of CCND1 genotype to individual triple negative breast cancer susceptibility. Materials: In all, 2464 native Taiwan subjects consist of 1232 breast cancer cases and 1232 controls were enrolled in a hospital-based, case-control study. CCND1 A870G (rs9344) genotyping was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Risk-stratified analyses correlated genotype and age-related characteristics of breast cancer subgroups. Results: No significant difference was found between patient and control groups in distribution of genotypic and allelic frequencies in CCND1 genotype, yet CCND1 A870G (rs9344) GG genotype was far less prevalent in breast cancer patients younger than 55 years (OR=0.62, 95%CI=0.43-0.89, P=0.0362), with first menarche earlier than 12.2 years (OR=0.61, 95% CI=0.42-0.87, P=0.0241), with menopause earlier than 49.0 years (OR=0.57, 95%CI=0.39-0.82, P=0.0093), or showing triple-negative breast cancer (OR=0.28, 95%CI=0.13-0.62, P=0.0006). Such valuable findings suggest CCND1 A870G (rs9344) as a predictive marker for triple negative breast cancer in Taiwanese women; the authors sincerely hope these help us fight the toughest subtype in clinical management.

Evaluation of the contribution of cyclooxygenase 2 genotypes to breast cancer in Taiwan.

Overexpression of cyclooxygenase 2 (COX-2) has been suggested to be associated with breast carcinogenesis. The aim of the present study was to evaluate the contribution of genotypic polymorphisms in COX-2 to breast cancer risk of Taiwanese females. In total, 1,232 breast cancer patients and 1,232 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Six polymorphic variants of COX-2, including G-1195A (rs689466), G-765C (rs20417), T8473C (rs5275), intron 1 (rs2745557), intron 5 (rs16825748) and intron 6 (rs2066826) were examined. The results showed that the GC genotype of COX-2, G-765C was associated with a lower risk compared to the wild-type GG genotype (odds ratio(OR)=0.66, 95% confidence interval(CI)=0.53-0.83, p=0.0005). The C allele of COX-2 G-765C was significantly more frequently found in controls than in cancer patients (p=0.0006). In addition, the OR of the GG/AG+AA, GC/GG and GC/AG+AA at G-765C/Intron 1 combined genotypes compared to wild-type GG/GG genotype were 0.79 (95%CI=0.66-0.96; p=0.0166), 0.61 (95%CI=0.48-0.78; p=0.0001), and 0.71 (95%CI=0.36-1.37; p=0.3040), respectively. As for the combination of G-765C and intron 6, the OR of the GG/AG+AA, GC/GG and GC/AG+AA combined genotypes compared with wild-type GG/GG reference genotype were 0.79 (95%CI=0.62-1.01; p=0.0561), 0.63 (95%CI=0.50-0.81; p=0.0003), and 0.68 (95%CI=0.38-1.21; p=0.1897), respectively. Our results indicate that the C allele of COX-2, G-765C was associated with a decreased risk of breast cancer in Taiwan, and could serve as an early detection and predictive marker for breast cancer risk.

EORTC QLQ-BM22 quality of life evaluation and pain outcome in patients with bone metastases from breast cancer treated with zoledronic acid.

BACKGROUND: We assessed the effect of zoledronic acid on quality of life (QOL) and pain outcome in breast cancer patients with bone metastases using the European Organization for Research and Treatment of Cancer bone metastases module (EORTC QLQ-BM22). PATIENTS AND METHODS: Three hundred sixty-six breast cancer patients receiving zoledronic acid for bone metastases from 13 Centers were prospectively enrolled. QOL was evaluated using the EORTC QLQ-BM22 and pain outcome were measured monthly with a Visual Analog Scale (VAS) score for 24 months. RESULTS: No significant change of functional scale (functional interference and psychosocial aspects) of the EORTC QLQ-BM22 was reported. Significant reduction of the symptom scale was noted after treatment compared with the baseline. The painful site subscale was significantly reduced during the first 12 months, with the exception the 6-month follow-up of point. Pain characteristics subscale was also significantly lower from the 2-month time point onwards. VAS scores indicated a significant reduction in pain over the course of the study to the 22-month time point follow-up compared to the baseline. CONCLUSION: Zoledronic acid treatment improved QOL of breast cancer patients with bone metastases by relieving bone pain.

Evaluation of the contribution of methylenetetrahydrofolate reductase genotypes to Taiwan breast cancer.

The aim of the present study was to evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and its interaction with early-onset breast cancer risk in Taiwan. Two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed and their joint effects with individual age- and estrogen-related factors on breast cancer risk were discussed. In total, 1,232 patients with breast cancer and 1,232 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The MTHFR C677T genotype, but not the A1298C, was differently distributed between cancer and control groups. The T allele of MTHFR C677T was significantly more frequently found in controls than in patients with cancer. In addition, females carrying MTHFR C677T CT or TT genotypes had a higher odds ratio of 1.21 (95% confidence interval=1.03-1.42, p=1.85E-5) for breast cancer, especially before the age of 45.4 years (odds ratio=1.51 and 95% confidence interval=1.20-1.90). Our results indicate that MTHFR C677T T allele was associated with increased risk of breast cancer in Taiwan, especially in cases who were 45.4 old or younger and with earlier menarche age (<12.2 years).

Quality of life assessment in Taiwanese patients with bone metastases from breast cancer receiving zoledronic acid.

BACKGROUND: The current study aimed to examine the impact of zoledronic acid therapy on health-related quality of life (HRQoL) in Taiwanese patients with bone metastases from breast cancer. PATIENTS AND METHODS: Patients with bone metastases from breast cancer who received zoledronic acid according to the standards of care were enrolled in this observational phase IV study. HRQoL was measured monthly using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (QLQ-C30) and the breast cancer-specific module (BR-23) for 24 months. RESULTS: A total of 366 patients from 13 centers were enrolled. QLQ C-30 demonstrated that zoledronic acid improved the HRQoL in different aspects. In particular, a significant reduction of pain in the first 14 months and the 22-month follow-up was reported by patients. QLQ-BR23 indicated improved future perspective and breast symptom scores over the course of the study. CONCLUSION: These data confirm the HRQoL benefits and safety of zoledronic acid in Taiwanese patients with bone metastases from breast cancer.