Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab: a multicenter retrospective observational study (JBCRG-C03 study)

We investigated the disease-free survival (DFS) of HER2-positive primary breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, as well as predictive factors for DFS and pathologic response. Data from 829 female patients treated between 2001 and 2010 were collected from 38 institutions in Japan. Predictive factors were evaluated using multivariate analyses. The 3-year DFS rate was 87 % [95 % confidence interval (CI) 85–90]. The pathologic complete response (pCR: ypT0/is + ypN0) rate was 51 %. The pCR rate was higher in the ER/PgR-negative patients than in the ER/PgR-positive patients (64 vs. 36 %, P < 0.001). Patients with pCR showed a higher DFS rate than patients without pCR (93 vs. 82 %, P < 0.001). Multivariate analysis revealed three independent predictors for poorer DFS: advanced nodal stage [hazard ratio (HR) 2.63, 95 % CI 1.36–5.21, P = 0.004 for cN2–3 vs. cN0], histological/nuclear grade 3 (HR 1.81, 95 % CI 1.15–2.91, P = 0.011), and non-pCR (HR 1.98, 95 % CI 1.22–3.24, P = 0.005). In the ER/PgR-negative dataset, non-pCR (HR 2.63, 95 % CI 1.43–4.90, P = 0.002) and clinical tumor stage (HR 2.20, 95 % CI 1.16–4.20, P = 0.017 for cT3–4 vs. cT1–2) were independent predictors for DFS, and in the ER/PgR-positive dataset, histological grade of 3 (HR 3.09, 95 % CI 1.48–6.62, P = 0.003), clinical nodal stage (HR 4.26, 95 % CI 1.53–13.14, P = 0.005 for cN2–3 vs. cN0), and young age (HR 2.40, 95 % CI 1.12–4.94, P = 0.026 for ≤40 vs. >40) were negative predictors for DFS. Strict pCR (ypT0 + ypN0) was an independent predictor for DFS in both the ER/PgR-negative and -positive datasets (HR 2.66, 95 % CI 1.31–5.97, P = 0.006 and HR 3.86, 95 % CI 1.13–24.21, P = 0.029, respectively). These results may help assure a more accurate prognosis and personalized treatment for HER2-positive breast cancer patients.     

The impact of cyclin D1 overexpression on the prognosis of ER-positive breast cancers: a meta-analysis

Cyclin D1 (CCND1), a key regulator of cell cycle progression, is overexpressed in many human cancers, including breast cancer. However, the impact of CCND1 overexpression in these cancers remains unclear and controversial. We conducted a systematic literature search in PubMed and EMBASE with the search terms “cyclin D1”, “CCND1”, “breast cancer”, “prognosis”, and potential studies for analysis were selected. Studies with survival data, including progression-free survival (PFS), overall survival (OS) or metastasis-free survival (MFS), were included in this meta-analysis. A total of 33 studies containing 8,537 cases were included. The combined hazard risk (HR) and its 95 % confidence interval (CI) of OS, PFS and MFS were 1.13 (95 % CI 0.87–1.47; P = 0.35), 1.25 (95 % CI 0.95–1.64; P = 0.12), and 1.04 (95 % CI 0.80–1.36; P = 0.76), respectively, for primary breast cancer patients with tumors exhibiting CCND1 overexpression. Interestingly, the impact of CCND1 expression on OS was a 1.67-fold (95 % CI 1.38–2.02; P = 0.00) increased risk for ER-positive breast cancer patients. However, CCND1 overexpression exhibited no association with the PFS or OS of patients who received epirubicin-based neoadjuvant chemotherapy, for which the P values were 0.63 and 0.47, respectively. In summary, CCND1 overexpression impacts the prognosis of ER-positive breast cancer patients, but not patients with unselected primary breast cancer or patients treated with neoadjuvant chemotherapy.     

Reproductive factors and the risk of breast cancer in old age: a Norwegian cohort study

Reproductive factors, including early age at menarche, late age at first birth, low parity, and late age at menopause, are associated with increased risk of breast cancer, but it is not clear to which degree the associations persist into old age. Altogether 58,426 Norwegian women born between 1886 and 1928 were followed up for breast cancer incidence from 1961 to 2008. Associations of reproductive factors with breast cancer risk were analyzed separately for the age intervals 55–69 and 70 years and older, using Cox regression. The associations were of similar strength in the two age strata. At 70 years and later, hazard ratios (HR) for the following comparisons were found: late (≥17 years) versus early (<13 years) age at menarche [HR 0.79, 95 % confidence interval (CI): 0.62, 1.01, P for trend <0.001]; late (≥35 years) versus early (<20 years) age at first birth (HR 1.54, 95 % CI: 1.13, 2.11, P for trend <0.001); high (≥5) versus low (1) parity (HR 0.68, 95 % CI: 0.54, 0.86, P for trend = 0.001) and late (50–54 years) versus early (<45 years) age at menopause (HR 1.44, 95 % CI: 1.10, 1.90, P for trend = 0.002). These findings suggest that reproductive events may have life-long effects on breast cancer risk.     

The KL-VS sequence variant of Klotho and cancer risk in BRCA1 and BRCA2 mutation carriers

Klotho (KL) is a putative tumor suppressor gene in breast and pancreatic cancers located at chromosome 13q12. A functional sequence variant of Klotho (KL-VS) was previously reported to modify breast cancer risk in Jewish BRCA1 mutation carriers. The effect of this variant on breast and ovarian cancer risks in non-Jewish BRCA1/BRCA2 mutation carriers has not been reported. The KL-VS variant was genotyped in women of European ancestry carrying a BRCA mutation: 5,741 BRCA1 mutation carriers (2,997 with breast cancer, 705 with ovarian cancer, and 2,039 cancer free women) and 3,339 BRCA2 mutation carriers (1,846 with breast cancer, 207 with ovarian cancer, and 1,286 cancer free women) from 16 centers. Genotyping was accomplished using TaqMan^® allelic discrimination or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed within a retrospective cohort approach, stratified by country of origin and Ashkenazi Jewish origin. The per-allele hazard ratio (HR) for breast cancer was 1.02 (95% CI 0.93–1.12, P = 0.66) for BRCA1 mutation carriers and 0.92 (95% CI 0.82–1.04, P = 0.17) for BRCA2 mutation carriers. Results remained unaltered when analysis excluded prevalent breast cancer cases. Similarly, the per-allele HR for ovarian cancer was 1.01 (95% CI 0.84–1.20, P = 0.95) for BRCA1 mutation carriers and 0.9 (95% CI 0.66–1.22, P = 0.45) for BRCA2 mutation carriers. The risk did not change when carriers of the 6174delT mutation were excluded. There was a lack of association of the KL-VS Klotho variant with either breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.     

Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers

The purpose of this article is to evaluate the prognostic value of androgen receptor (AR) expression in patients with estrogen receptor (ER)-positive breast cancer, treated with endocrine therapy, with or without the addition of chemotherapy. A consecutive series of 953 patients with ER-positive breast cancer, treated between 1998 and 2003, was selected. Repeated immunohistochemistry confirmed the expression of ER in the tumor of 938 patients. AR expression was measured by immunohistochemistry. The Kaplan–Meier method, logrank test and multivariate Cox models were used to explore the impact of AR expression on time to relapse (TTR) and disease specific survival (DSS) in all patients and in subgroups treated with chemo-endocrine therapy or endocrine therapy alone. AR immunoreactivity was assessable in 859 tumors and positive in 609 (70.9%). AR expression was a significant marker of good prognosis for TTR (P = 0.001) and DSS (P < 0.001). This effect was particularly evident in the group of patients receiving chemo-endocrine therapy (TTR (P = 0.015) and DSS (P < 0.001)). Cox models confirmed AR as an independent variable for both TTR (P = 0.003, HR 0.444, 95%CI 0.258–0.765) and DSS (P < 0.001, HR 0.135, 95%CI 0.054–0.337). Thus, we focused on ER-positive luminal B breast cancer that may be selected for chemotherapy because of their more aggressive immunophenotype. In this subset AR expression identified a group of patients with better prognosis for TTR (P = 0.017, HR 0.521, 95%CI 0.306–0.888) and DSS (P = 0.001, HR 0.276, 95% CI 0.130–0.588). AR expression is an independent prognostic factor of better outcome in patients with ER-positive breast cancers.     

Adolescent physical activity in relation to breast cancer risk

Adolescent physical activity may protect against premenopausal breast cancer. Whether it also prevents postmenopausal breast cancer, and whether associations are independent of adult activity, is unclear. We evaluated this association among 75,669 women in the Nurses’ Health Study II. In 1997, participants reported strenuous, moderate, and walking activity (hours/week) at ages 12–13, 14–17, 18–22, and 23–29 years. We estimated metabolic equivalent task hours (MET-h)/week. Participants also reported current physical activity over follow-up. Breast cancer diagnoses (n = 2,697; premenopausal = 1,351; postmenopausal = 965) through 2011 were reported by participants and confirmed with medical records. We additionally stratified analyses by median age at diagnosis. In Cox proportional hazards models adjusted for adolescent characteristics, physical activity from ages 14–22 was modestly inversely associated with premenopausal breast cancer [e.g., hazard ratio (HR) comparing 72+ to <21 MET-h/week 0.81 (95 % confidence interval (CI) 0.69–0.95; p-trend = 0.10) for ages 14–17 and 0.85 (95 % CI 0.71–1.02; p-trend = 0.06 for ages 18–22]. However, adjustment for adult activity and additional breast cancer risk factors attenuated the associations [ages 14–17: 0.85 (95 % CI 0.73–1.00; p-trend = 0.33)]. Associations were stronger among women diagnosed at younger ages [e.g., ages 18–22, HR 0.77 (95 % CI 0.60–0.99; p-trend = 0.05) for women diagnosed before 46.9 years; HR 1.02 (95 % CI 0.79–1.32; p-trend = 0.94) for those diagnosed at/after 46.9 years]. Early life physical activity was not associated with postmenopausal breast cancer. Overall, adolescent physical activity was not associated with breast cancer risk. However, we observed a suggestive inverse association of physical activity at ages 14–22 years with premenopausal breast cancer.     

Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in the Cypriot population

Inability to correctly repair DNA damage is known to play a role in the development of breast cancer. Single nucleotide polymorphisms (SNPs) of DNA repair genes have been identified, which modify the DNA repair capacity, which in turn may affect the risk of developing breast cancer. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 62 SNPs in 29 genes in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. Five SNPs were associated with breast cancer. SNPs rs13312840 and rs769416 in the NBS1 gene were associated with a decrease in breast cancer risk (OR TT vs. TC/CC = 0.58; 95% CI, 0.37–0.92; P = 0.019 and OR GG vs. GT/TT = 0.23, 95% CI 0.06–0.85, P = 0.017, respectively). The variant allele of MRE11A rs556477 was also associated with a reduced risk of developing the disease (OR AA vs. AG/GG = 0.76; 95% CI, 0.64–0.91; P = 0.0022). MUS81 rs545500 and PBOV1 rs6927706 SNPs were associated with an increased risk of developing breast cancer (OR GG vs. GC/CC = 1.21, 95% CI, 1.02–1.45; P = 0.031; OR AA vs. AG/GG = 1.53, 95% CI, 1.07–2.18; P = 0.019, respectively). Finally, haplotype-based tests identified significant associations between specific haplotypes in MRE11A and NBS1 genes and breast cancer risk. Further large-scale studies are needed to confirm these results.     

Long-term prognosis of early-onset breast cancer in a population-based cohort with a known BRCA1/2 mutation status

All women in the South Sweden Health Care Region with breast cancer diagnosed aged less than 41 during the period between 1990 and 1995 were contacted in 1996 and offered germline mutation analysis of the BRCA1 and BRCA2 genes. Mutation carriers (n = 20) were compared with noncarriers (n = 201) for overall survival (OS) and risk of contralateral breast cancer (CBC). Mutation carriers were younger at diagnosis and more likely to have ER-negative, PgR-negative and grade III tumors. Median follow-up was 19 years. The 5-, 10-, 15-, and 20-year OS were 60, 45, 39, and 39 % for mutation carriers and 82, 70, 59, and 53 % for noncarriers, respectively (5-year log-rank P = 0.013; 10-year P = 0.008; 15-year P = 0.020; and 20-year P = 0.046). In univariable analysis, there was a trend for an inferior OS for mutation carriers (HR 1.8; 95 % CI 1.0–3.3). When stratified for use of (neo)adjuvant chemotherapy, an inferior OS was significant only for the subgroup of patients who did not receive chemotherapy (HR 3.0; 95 % CI 1.2–7.7). In multivarible analysis, BRCA1/2 mutation status was a significant predictor of OS when adjusting for tumor stage, age, and use of chemotherapy, but not when ER status was also included in the model. The 15-year cumulative risk of CBC was 53 % for mutation carriers and 10 % for noncarriers (HR 5.9; 95 % CI 1.9–18.6); among the noncarriers the risks were 5, 22, and 30 % for patients without close relatives having breast cancer, with second-degree relatives having breast cancer, and with firstdegree relatives with breast cancer, respectively. In conclusion, the poor prognosis of young BRCA1/2 mutation carriers with breast cancer is mainly explained by the prevalent occurrence of negative prognostic factors rather than mutation status per se, and can to at least some extent be abrogated by the use of chemotherapy.     

Triple-negative breast cancer: the impact of guideline-adherent adjuvant treatment on survival—a retrospective multi-centre cohort study

Triple-negative breast cancer (TNBC) (ER?/PGR?/erb-2?) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2? breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27–2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17–3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8–80.8%] vs. 86.5% [95% CI: 84.6–88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9–81.8%] vs. 86.0% [95% CI: 84.1–87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number of guideline violations.     

Validation of 70-gene prognosis signature in node-negative breast cancer

Purpose The 70-gene prognosis signature (van’t Veer et al., Nature 415(6871):530–536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. Methods We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999–2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). Results The 5-year OS was 82 ± 5% in poor (48%) and 97 ± 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2–9.6; P = 0.021). The 5-years DMFP was 78 ± 6% in poor and 98 ± 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6–20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 ± 5% and 94 ± 3% (HR 10.7; 95% CI 3.9–30; P < 0.01), respectively. The DMFP was 50 ± 6% in poor and 86 ± 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5–12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. Conclusion The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.     

Primary tumor classification according to methylation pattern is prognostic in patients with early stage ER-negative breast cancer

Breast cancer patients with similar clinical stage may experience different disease outcomes. Aberrant DNA methylation of primary breast tumors can have impact on the clinical outcome. This study aimed to assess clinical utility of tumor-specific methylated sequences (MINT17, 31) and tumor-related gene (RARβ2) methylation classification in primary breast tumors. Absolute quantitative assessment of methylated alleles (AQAMA) was used to determine the methylation index (MI) of MINT17, MINT31, and RARß2 in 242 primary tumors of early stage breast cancer patients. Patients were classified into three methylation groups: meth-N, with normal methylation levels of all biomarkers; meth-L, with one biomarker hypermethylation; and meth-H, with hypermethylation of >1 biomarker. Disease outcome of methylation groups was compared during follow-up. MI of all biomarkers was successfully obtained in 237 tumors of which 79 (33%) were classified as meth-N, 86 (36%) as meth-L, and 72 (30%) as meth-H. Meth-H status was a risk factor for distant recurrence (DR) (log-rank P = 0.007) and shorter disease-free survival (DFS) (log-rank P = 0.039). Methylation classification had strongest prognostic value for patients with ER-negative tumors. In multivariate analysis (n = 222), ER-negative meth-H patients had a 4.1-fold increased risk of DR (95% CI 1.80–9.59; meth-N HR 1.0, P = 0.001), a 4.2-fold increased risk of overall recurrence (OR) (95% CI 1.88–9.47; meth-N HR 1.0, P = 0.001), and a 3.1-fold shorter DFS (95% CI 1.57–5.98; meth-N HR 1.0, P = 0.003). Methylation classification of primary breast cancer is an independent prognostic factor for disease outcome in patients with ER-negative tumors. The study’s findings will have to be confirmed in an independent dataset.     

Factors predicting efficacy and adverse effects of enzalutamide in Japanese patients with castration-resistant prostate cancer: results of retrospective multi-institutional study

Background

We aimed to evaluate the factors predicting efficacy and adverse effects of enzalutamide in patients with castration-resistant prostate cancer.

Methods

We retrospectively evaluated data on 345 patients who had received enzalutamide for castration-resistant prostate cancer in 20 hospitals (Kyoto University Hospital and other satellite hospitals). Cox proportional hazards regression analysis was performed to identify factors predicting prostate-specific antigen (PSA) progression after enzalutamide treatment and logistic regression analysis for those associated with development of adverse effects.

Results

PSA titers decreased by >50 % in 197 patients (57 %). The median PSA progression free survival was 163 days. Gleason score >8 (HR 2.078, 95 % CI 1.37–3.153, P = 0.00058), performance status ≥1 (HR 2.292, 95 % CI 1.463–3.592, P = 0.000296), presence of bone metastasis (HR 1.774, 95 % CI 1.019–3.090, P = 0.0429), visceral metastasis (HR 2.127, 95 % CI 1.215–3.722, P = 0.00823), previous steroid treatment (HR 1.780, 95 % CI 1.207–2.626, P = 0.00361) and docetaxel treatment (HR 1.602, 95 % CI 1.051–2.442, P = 0.0284) significantly predicted the efficacy of enzalutamide. Adverse effects, including fatigue or appetite loss, occurred in 169 patients (49 %), 48 (18 %) of whom stopped enzalutamide. Age >75 years (HR 1.980, 95 % CI 1.270–3.09, P = 0.00246) and lower enzalutamide dose (HR 0.437, 95 % CI 0.255–1.270, P = 0.00249) were significantly associated with development of adverse effects.

Conclusions

Enzalutamide treatment is effective in patients with castration-resistant prostate cancer with low Gleason scores, good performance status, without bone or visceral metastasis and no prior steroid or docetaxel treatment. Lower doses of enzalutamide decrease the incidence of adverse effects, especially in older patients.

     

Prognosis of gastric carcinoma patients aged 85 years or older who underwent surgery or who received best supportive care only

Background

There is controversy regarding strategies for treating very elderly patients with gastric carcinoma. We aimed to assess survival after surgery in very elderly patients according to their clinical characteristics.

Methods

Gastric cancer patients aged ≥85 years were retrospectively reviewed. There were no significant differences in clinical characteristics between 58 patients with curative resection (OP group) and 32 patients with best supportive care alone (BSC group) in cancer stage IA–IIIC and with a performance status of 0–3.

Results

Overall survival (OS) was significantly better in the OP group than in the BSC group in females [hazard ratio (HR) 0.27, 95 % confidence interval (CI) 0.12–0.57, P < 0.001] but not in males (HR 0.71, 95 % CI 0.35–1.49, P = 0.35). OS was significantly better in the OP group in patients aged 85–89 years (HR 0.44, 95 % CI 0.25–0.78, P = 0.006) but not in patients aged ≥90 years (HR 0.47, 95 % CI 0.12–1.66, P = 0.24). OS was significantly better in the OP group in patients with stage IB–IIIC cancer (HR 0.29, 95 % CI 0.14–0.58, P < 0.001) but not in patients with stage IA cancer (HR 0.52, 95 % CI 0.21–1.27, P = 0.15).

Conclusions

Females, patients aged 85–89 years, and patients with stage IB–IIIC cancer had significantly better OS with surgery than without. For males, patients aged ≥90 years, or stage IA patients, the decision to perform surgery should be carefully made, and BSC might be an optimal strategy.     

CYP2D6 polymorphisms influence tamoxifen treatment outcomes in breast cancer patients: a meta-analysis

Purpose

To evaluate whether breast cancer (BC) patients with CYP2D6 gene variation have different clinical tamoxifen (TAM) treatment outcomes to those with normal function of CYP2D6.

Methods

Systematic searches of the PubMed up to February 21, 2013, were retrieved. The study end points were disease-free survival (DFS) and overall survival (OS). Fixed or random-effects meta-analytical models were used to calculate summary hazard ratio (HR) and corresponding 95 % confidence intervals (CIs). Meta-regression, Galbraith plots, subgroup analysis, and sensitivity analysis were also performed.

Results

A total of 11,701 BC patients from 20 trials were included. Compared with reduced CYP2D6 function, normal function was associated with a trend toward improved DFS (HR = 1.37, 95 % CI 1.12–1.69, P = 0.002) and OS (HR = 1.25, 95 % CI 1.03–1.50, P = 0.021). We found significant heterogeneity between studies. When the analysis was stratified into subgroups, significantly worse DFS was found in the groups of intermediate metabolizer versus extensive metabolizer (HR = 1.65, 95 % CI 1.04–2.64, P = 0.035), Asian population (HR = 3.29, 95 % CI 1.64–6.63, P = 0.001), 5 years TAM treatment duration (HR = 1.59; 95 % CI 1.14–2.22, P = 0.006), concomitant chemotherapy (HR = 1.35, 95 % CI 1.04–1.76, P = 0.025), and TAM alone (HR = 1.44, 95 % CI 1.44–2.06, P = 0.045). With respect to OS, no significant association was demonstrated in stratified analyses.

Conclusions

We concluded that CYP2D6 polymorphisms may influence tamoxifen treatment outcomes of DFS in BC patients.     

Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers

It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case–control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20–1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99–1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14–1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03–1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79–1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.     

Impact of local surgical treatment on survival in young women with T1 breast cancer: long-term results of a population-based cohort

The aim of this study was to analyze the effect of the type of local surgical treatment on survival in young women aged less than 40 years with T1 breast cancer. We analyzed data from 3,512 patients aged ≤40 years old who were diagnosed with T1 breast cancer from the Korean Breast Cancer Registry database between January 1988 and December 2006 and underwent either breast-conserving therapy (BCT) or mastectomy. The overall survival (OS) and breast-cancer-specific survival (BCSS) were compared between BCT and mastectomy. Of the 3,512 patients analyzed, 1,951 (55.6 %) underwent BCT, and 1,561 (44.4 %) underwent mastectomy. The median follow-up period was 111.0 (79.0–131.5) months. Overall, the 10-year OS rates for BCT and mastectomy were 95 and 92.1 %, respectively (p = 00004), and the 10-year BCSS rates for BCT and mastectomy patients were 96.9 and 94.9 %, respectively (p = 0.12). In node-negative patients, no significant difference was observed in either the OS (adjusted hazard ratio [HR] 1.072; 95 % CI, 0.750–1.5332, p = 0.704) or BCSS (adjusted HR 0.988; 95 % CI, 0.620–1.574, p = 0.960) rate between the BCT and mastectomy groups. In node-positive patients, no significant difference was observed in the OS (adjusted HR 1.634; 95 % CI, 0.982–2.272, p = 0.59) and BCSS (adjusted HR 1.410; 95 % CI, 0.755–2.633, p = 0.281) rates between the BCT and mastectomy groups. In this large, population-based analysis of young women with T1 breast cancer, the OS and BCSS were not different between BCT and mastectomy.     

Neutrophil-to-lymphocyte Ratio,Platelet-to-lymphocyte Ratio,and C-reactive Protein as New and Simple Prognostic Factors in Patients With Metastatic Renal Cell Cancer Treated With Tyrosine Kinase Inhibitors: A Systemic Review and Meta-analysis

Background

Inflammation plays a crucial role in cancer development. In this study, we evaluate the prognostic values of systemic inflammation markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) for the progression-free survival and overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

Impact of genetic variability and treatment-related factors on outcome in early breast cancer patients receiving (neo-) adjuvant chemotherapy with 5-fluorouracil,epirubicin and cyclophosphamide,and docetaxel

To assess the impact of patient-related factors, including genetic variability in genes involved in the metabolism of chemotherapeutic agents, on breast cancer-specific survival (BCSS) and recurrence-free interval (RFI). We selected early breast cancer patients treated between 2000 and 2010 with 4–6 cycles of (neo-)adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) or 3 cycles FEC followed by 3 cycles docetaxel. Tumor stage/subtype; febrile neutropenia and patient-related factors such as selected single nucleotide polymorphisms and baseline laboratory parameters were evaluated. Multivariable Cox regression was performed. Of 991 patients with a mean follow-up of 5.2 years, 152 (15.3 %) patients relapsed and 63 (6.4 %) patients died. Advanced stage and more aggressive subtype were associated with poorer BCSS and RFI in multivariable analysis (p < 0.0001). Associations with worse BCSS in multivariable analysis were: homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (hazard ratio [HR] 30.4; 95 % confidence interval [CI] 6.1–151.5; p < 0.001) and higher white blood cell count (WBC) (HR 1.2; 95 % CI 1.0–1.3; p = 0.014). The GT genotype of the ABCB1 variant rs2032582 was associated with better BCSS (HR 0.5; 95 % CI 0.3–0.9, p = 0.021). Following associations with worse RFI were observed: higher WBC (HR 1.1; 95 % CI 1.0–1.2; p = 0.026), homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (HR 10.9; 95 % CI 2.5–47.9; p = 0.002), CT genotype of the CYBA variant rs4673 (HR 1.8; 95 % CI 1.2–2.7; p = 0.006), and G-allele homozygosity for the UGT2B7 variant rs3924194 (HR 3.4; 95 % CI 1.2–9.7, p = 0.023). Patient-related factors including genetic variability and baseline white blood cell count, impacted on outcome in early breast cancer.     

Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women’s Health Initiative observational study

An increased risk of breast cancer has been reported in patients with non-melanomatous skin cancer (NMSC), but this association has not been studied in a large, multi-geographic population. We utilized data from the Women’s Health Initiative observational study to assess whether history of NMSC is associated with breast cancer risk. This analysis included 70,246 postmenopausal White and Hispanic women aged 50–79, in which 4,247 breast cancer cases were identified over a mean (SD) of 11.3 (3.2) years. Baseline information was collected on demographics, medical history, sun exposure, and vitamin D intake. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs). The relationship between NMSC and breast cancer was examined as a time-dependent exposure using updated information on NMSC gathered during follow-up visits. All statistical tests were two sided. There were 5,595 women diagnosed with NMSC at study entry. The annualized rate of breast cancer was 0.64 % among women with a history of NMSC and 0.55 % among women with no history of NMSC. The multivariable-adjusted HR for breast cancer among women with a history of NMSC versus no history of NMSC was 1.07 (95 % CI 0.95–1.20, P = 0.27). Further evaluation stratified by tumor characteristics showed an increased risk of lymph node-positive disease, HR = 1.30 (95 % CI 1.01–1.67, P = 0.04), and regional-stage disease, HR = 1.33 (95 % CI 1.05–1.70, P = 0.02), among women with NMSC. There was no significant overall association between NMSC and breast cancer; however, there was an increased risk of more advanced-stage breast cancer which needs further exploration.