Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ

We aimed to identify clinicopathologic factors associated with local recurrence (LR) in a large population of DCIS patients treated with breast-conserving therapy between 1990–2001 in three health plans. Regression methods were used to estimate relative risks (RR) of LR. Among 2,995 patients, 325 had a LR [10.9 %; median follow-up 4.8 years (range 0.5–15.7)]. After adjusting for health plan and treatment, risk of LR was increased among women <45 years (RR = 2.1, 95 % CI 1.5–2.8), African-Americans (RR = 1.6; 95 % CI 1.1–2.1) and those with DCIS detected because of signs/symptoms (RR = 1.6; 95 % CI 1.2–2.0). After also adjusting for age and diagnosis year, pathologic features associated with increased LR were larger lesion size (RR = 2.9 for ≥20 low power fields of DCIS; 95 % CI 1.6–5.6) and involved (RR = 2.9; 95 % CI 1.6–5.2), or close margins (RR = 2.4; 95 % CI 1.6–3.8). Presentation with symptoms/signs was associated with increased risk of invasive recurrence; while African-American race, larger tumor size, and involved/close tumor margins were more strongly associated with increased risk of DCIS recurrence. Our findings suggest some risk factors differ for non-invasive and invasive LRs and that most factors are only moderately associated with increased LR risk. Future research efforts should focus on non-clinicopathologic factors to identify more powerful risk factors for LR.     

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.     

High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer

The purpose of the study was to compare breast-conserving therapy (BCT) and mastectomy (M) in BRCA1/2 mutation carriers. Women with invasive breast cancer and a pathogenic mutation in BRCA1 or BRCA2 were included in the study (n = 162). Patients treated with BCT (n = 45) were compared with patients treated with M (n = 118). Endpoints were local recurrence as first recurrence (LR), overall survival (OS), breast cancer death, and distant recurrence. Cumulative incidence was calculated in the presence of competing risks. For calculation of hazard ratios and for multivariable analysis, cause-specific Cox proportional hazards regression was used. Compared to M, BCT was associated with an increased risk of LR in univariable analysis (HR 4.0; 95 % CI 1.6–9.8) and in multivariable analysis adjusting for tumor stage, age, and use of adjuvant chemotherapy (HR 2.9; CI 1.1–7.8). Following M, all local recurrences were seen in the first 5 years after breast cancer diagnosis. Following BCT, the rate of LR continued to be high also after the first 5 years. The cumulative incidence of LR in the BCT group was 15, 25, and 32 % after 5, 10, and 15 years, respectively. There were no significant differences between BCT and M for OS, breast cancer death, or distant recurrence. BRCA1/2 mutation carriers treated with BCT have a high risk of LR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing could influence choice of treatment.     

Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patients. This study included a consecutive series of 536 patients ≤40 years of age at diagnosis with pathological T1N0-3M0 BC, treated between 1989 and 2005. A multistate survival model was used to evaluate the influences of local treatment and LRR on DMD, adjusted for potential prognostic factors. Patients were treated with mastectomy (N = 213) or BCT (N = 323). Median age at diagnosis was 36.3 years, with a median follow-up of 9.0 years. The 10-year actuarial cumulative incidence of DMD was 30.6 % after mastectomy and 26.3 % after BCT (P = 0.04). In total, 81 (15 %) LRRs were observed. After BCT, patients had a threefold higher risk of LRR than after mastectomy (HR 2.9; 95 % CI 1.6–5.3). Patients with LRR had a higher risk of DMD compared with patients without LRR (HR 5.5; 95 % CI 2.1–14.5). However, BCT was not negatively associated with DMD-after-LRR (HR 0.47; 95 % CI 0.2–1.1, BCT vs mastectomy). In conclusion, although LRR significantly affected DMD, the increased risk of LRR after BCT compared with mastectomy did not lead to a worse DMD outcome in BC patients ≤40 years of age.     

Local recurrence following breast-conserving treatment in women aged 40 years or younger: Trends in risk and the impact on prognosis in a population-based cohort of 1143 patients

AimTo evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a large, population-based cohort of women aged ?40 years with early-stage breast cancer.MethodsAll women (n = 1143) aged ?40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast.ResultsAfter a median follow-up of 8.5 (0.1–24.6) years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988–1998, 1999–2005 and 2006–2010 were 9.8% (95% confidence interval (CI) 7.1–12.5), 5.9% (95% CI 3.2–8.6) and 3.3% (95% CI 0.6–6.0), respectively (p = 0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95% CI 0.28–0.60; p < 0.0001). Patients who experienced an early isolated LR (?5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27–2.64; p = 0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74–2.08; p = 0.407).ConclusionLocal control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.     

Incidence of contralateral breast cancer in Japanese patients with unilateral minimum-risk primary breast cancer,and the benefits of endocrine therapy and radiotherapy

Background:

Tamoxifen is recommended as adjuvant endocrine therapy for patients with minimum-risk breast cancer. It is primarily effective at prevention of contralateral and ipsilateral breast cancer recurrence after breast-conserving surgery. The incidence of contralateral breast cancer and the absolute benefit of endocrine therapy among patients with unilateral minimum-risk breast cancer in Japan, where the incidence of breast cancer is low, are unknown.

Patients and methods

We retrospectively studied the incidence of contralateral breast cancer, and the efficacy of endocrine therapy, in a cohort of 2074 Japanese women with unilateral breast cancer whose primary tumor was pTis (n = 1905) or pT1mic (n = 169) (unknown for endocrine therapy, n = 4; unknown for radiotherapy, n = 2). We also assessed the efficacy of endocrine therapy and radiotherapy for prevention of ipsilateral and contralateral breast cancer recurrence in 1205 patients who underwent breast-conserving surgery (unknown for endocrine therapy, n = 2; unknown for radiotherapy, n = 2).

Results

The incidence of contralateral breast cancer per 1000 person-years was 5.1 (95 % confidence interval (CI), 3.7–7.1) among patients without endocrine therapy (n = 1364) and 3.6 (95 % CI 2.1–6.1) among those with endocrine therapy (n = 706). The incidence of ipsilateral breast cancer recurrence after breast-conserving surgery per 1000 person-years was 9.2 (95 % CI 6.5–13) among patients without endocrine therapy (n = 753) and 4.2 (95 % CI 2.2–8.1) among those with endocrine therapy (n = 450). The incidence of ipsilateral breast cancer recurrence after breast-conserving surgery per 1000 person-years was 9.9 (95 % CI 6.3–15.6) among patients without radiotherapy (n = 380) and 5.9 (95 % CI 3.9–9.0) among those with radiotherapy (n = 823).

Conclusion

The incidence of contralateral breast cancer among minimum-risk breast cancer patients in Japan, where the incidence of breast cancer is low, was similar to that in Western countries. Endocrine therapy is indicated for this population.     

Breast-cancer subtype,age, and lymph node status as predictors of local recurrence following breast-conserving therapy

Purpose/Objectives

Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT.

Methods

We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models.

Results

With a median follow-up of 106 months, 69 LRs (3 %) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B = 3.01, HER2 = 6.29, triple-negative [TNBC] = 4.72; p < 0.001 each), younger age (HR of oldest vs. youngest quartile = 0.43; p = 0.005), regional nodal involvement (HR for 4–9 involved nodes = 3.04; >9 nodes = 5.82; p < 0.01 for each), positive margins (HR 2.43; p = 0.005), and high grade (HR 5.37; p < 0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B = 2.64, HER2 = 5.42, TNBC = 4.32; p < 0.001 for each), younger age (HR for age >50 = 0.56; p = 0.01), and nodal disease (HR 1.06 per involved node; p < 0.004) were associated with LR. The 8-year risk of LR was 2.8 % for node-negative patients and 5.2 % for node-positive patients.

Conclusion

BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era.

     

Aesthetic result after breast-conserving therapy is associated with quality of life several years after treatment. Swedish women evaluated with BCCT.core and BREAST-Q™

Purpose

A gold standard for evaluation of aesthetic outcome after breast-conserving therapy (BCT) is still lacking. The BCCT.core software has been developed to assess aesthetic result in a standardised way. We aimed to study how the result of BCCT.core after BCT is associated with quality of life, measured with the BREAST-Q?, a validated questionnaire.

Methods

Women eligible for BCT were consecutively recruited between February 1st 2008 and January 31st 2012 (n = 653). Photographs of 310 women, taken one year after BCT, were evaluated using the BCCT.core software. The postoperative BCT module of the BREAST-Q? questionnaire was administered by mail and 348 questionnaires were returned (median 5.5 years after BCT). In all, 216 women had both BCCT.core results and completed BREAST-Q? questionnaires available.

Results

The results from the BCCT.core evaluation were: excellent n = 49 (15.8%); good n = 178 (57.4%); fair n = 73 (23.5%); poor n = 10 (3.2%). The median BREAST-Q? score for satisfaction with breasts was 66 [interquartile range (IQR) 57–80] and for psychosocial well-being 82 (IQR 61–100). Poor/fair results on BCCT.core were associated with Q-scores below median for both satisfaction with breasts [odds ratio (OR) 3.4 (confidence interval (CI) 1.7–6.8)] as well as for psychosocial well-being [OR 2.2 (CI 1.1–4.2)].

Conclusions

A statistically significant association between BCCT.core results one year after BCT and quality of life ratings using BREAST-Q? several years later is shown in this study. This implies that the BCCT.core may be valuable in BCT follow-up and used as a standardised instrument in the evaluation of aesthetic results.

     

Red and processed meat intake and risk of colorectal adenomas: a systematic review and meta-analysis of epidemiological studies

Background

Current evidence indicates that red and processed meat intake increases the risk of colorectal cancer; however, the association with colorectal adenomas is unclear.

Objective

To conduct a systematic review and meta-analysis of epidemiological studies of red and processed meat intake and risk of colorectal adenomas as part of the Continuous Update Project of the World Cancer Research Fund.

Design

PubMed and several other databases were searched for relevant studies from their inception up to 31 December 2011. Summary relative risks (RRs) were estimated using a random effects model.

Results

Nineteen case–control studies and seven prospective studies were included in the analyses. The summary RR per 100 g/day of red meat was 1.27 (95 % CI 1.16–1.40, I ² = 5 %, n = 16) for all studies combined, 1.20 (95 % CI 1.06–1.36, I ² = 0 %, n = 6) for prospective studies, and 1.34 (95 % CI 1.12–1.59, I ² = 31 %, n = 10) for case–control studies. The summary RR per 50 g/day of processed meat intake was 1.29 (95 % CI 1.10–1.53, I ² = 27 %, n = 10) for all studies combined, 1.45 (95 % CI 1.10–1.90, I ² = 0 %, n = 2) for prospective studies, and 1.23 (95 % CI 0.99–1.52, I ² = 37 %, n = 8) for case–control studies. There was evidence of a nonlinear association between red meat (p _nonlinearity < 0.001) and processed meat (p _nonlinearity = 0.01) intake and colorectal adenoma risk.

Conclusion

These results indicate an elevated risk of colorectal adenomas with intake of red and processed meat, but further prospective studies are warranted.     

Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy

PurposeThere is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We review the evidence on surgical margins in BCT for early-stage invasive breast cancer.MethodsMeta-analysis of studies reporting local recurrence (LR) relative to quantified final microscopic margin status and the threshold distance for negative margins. The proportion of LR was modelled using random effects logistic meta-regression.ResultsBased on 21 studies (LR in 1,026 of 14,571 subjects) the odds of LR were associated with margin status [model 1: odds ratio (OR) = 2.02 for positive/close versus negative; model 2: OR = 1.80 for close versus negative, 2.42 for positive versus negative (P < 0.001 both models)] but not with margin distance [1 mm versus 2 mm versus 5 mm (P > 0.10 both models)], adjusting for median follow-up time. However, there was weak evidence in both models that the odds of LR decreased as the threshold distance for declaring negative margins increased. This bordered significance in model 2 [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.75, 0.51 (P = 0.097 for trend)], and was not significant in model 1 [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.85, 0.58 (P = 0.11 for trend)] but was evident when one study (of women ? 40 years) was excluded from this model [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.72, 0.52 (P = 0.058 for trend)]: this trend was rendered insignificant by adjustment for the proportion of subjects receiving a radiation boost or the proportion of subjects receiving endocrine therapy.ConclusionsMargin status has a prognostic effect in all women treated for invasive breast cancer; increasing the threshold distance for declaring negative margins is weakly associated with reduced odds of LR, however adjustment for covariates (adjuvant therapy) removes the significance of this effect. Adoption of wider margins, relative to narrower widths, for declaring negative margins is unlikely to a have substantial additional benefit for long-term local control in BCT.     

Prognostic role of surgical margins in patients undergoing transoral robotic surgery after neo-adjuvant chemotherapy

PurposeTo define if positive and close surgical margins are associated to worse prognosis in patients who underwent transoral robotic surgery (TORS) after neoadjuvant chemotherapy (NCT).MethodsA retrospective cohort study was carried out at a tertiary referral center. The primary outcome was local-regional control (LRC), and the results were summarized with hazard ratios (HR) and 95% confidence intervals (CIs).ResultsA total of 308 patients (median age: 62.0, IQR: 55.0–68.2) were included. Univariable analysis showed a significant reduced LRC for patients with positive margins (HR = 1.82, 95% CI: 1.02–3.24). However, they were not associated with worse LRC after adjusting for adverse tumor variables (HR = 0.81, 95% CI: 0.40–1.65). ROC analysis was performed on 123 patients with negative margins (AUC: 0.54) measuring an optimal threshold of 1.25 mm (sensitivity = 60.0%; specificity = 50.5%). Univariable analysis showed non-significant differences between close and wide negative margins (HR = 1.44, 95% CI: 0.59–3.54).ConclusionsA positive surgical margin is not an independent predictor of tumor control and survival. A threshold of 1.25 mm was identified as the most appropriate to define close margins, but no difference was measured after distinguishing negative margins in close and wide margins.     

The role of surgical margin quality in myxofibrosarcoma and undifferentiated pleomorphic sarcoma

ObjectivesThe effect of margin quality as a barrier against infiltration of soft-tissue sarcomas (STSs) has been unclear. We aimed to investigate the effect of margin quantity and quality on local control for myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS).Methods278 patients with a localised MFS and UPS were studied. Margin quality was categorized into five types; type 1, pseudocapsule/reactive zone; type 2, fat/fibrofatty tissue; type 3, muscle; type 4, fascia; type 5, periosteum.ResultsThe 5-year cumulative LR incidence was 22% and 13% in patients with positive and 0.1–9.9 mm margins, respectively, but decreased to 3% with ≥10.0 mm margins (p = 0.009); the cumulative LR incidence was significantly lower in patients with ≥10.0 mm margins than those with positive margins (p = 0.033) but was not significantly different in those with 0.1–9.9 mm margins (p = 0.183). In patients with 0.1–9.9 mm margins, the cumulative LR incidence was affected by margin quality; type 4 and 5 provided an LR risk less than 5% (p < 0.001), which was similar to those with margins ≥10.0 mm. Combining these two factors together, the LR risk in patients with positive or 0.1–9.9 mm margins without fascia/periosteum was approximately 11 × higher than patients with 0.1–9.9 mm margins with fascia/periosteum or margins ≥10.0 mm (p = 0.002).ConclusionsA resection margin of 0.1–9.9 mm with fascia or periosteum provided a similar LR risk profile to ≥10 mm margins with any margin quality, which provided the lowest LR risk. The quality of fascial or periosteal tissue margins may be equivalent to a margin quantity of 10 mm as a barrier to LR.     

A phase II study of docetaxel and vinorelbine plus filgrastim for HER-2 negative, stage IV breast cancer: SWOG S0102

Docetaxel and vinorelbine have demonstrated Single-agent activity in breast cancer. Preclinical studies suggest potential synergy between these antitubulin chemotherapy agents. This study evaluates these drugs in combination in metastatic breast cancer. Taxane-naive patients with HER-2 negative, stage IV breast cancer without prior chemotherapy for metastatic disease, were eligible. Docetaxel (60 mg/m²) was given intravenously on Day 1, vinorelbine (27.5 mg/m²) intravenously on Days 8 and 15, and filgrastim on Days 2–21 of a 21-day cycle. The primary study outcome was one-year overall survival (OS), with secondary outcomes of progression-free survival (PFS), response rate (RR), and toxicity. Of 95 patients registered, 92 were eligible and received treatment. One-year OS was 74 % (95 % CI 64–82 %) with a median OS of 22.3 months (95 % CI 18.8–31.4 months). One-year PFS was 34 % (95 % CI 24–43 %) with median of 7.2 months (95 % CI 6.4–10.3). OS at 2 and 3 years were 49 % (95 % CI 38–59 %) and 30 % (95 % CI 21–40 %), respectively. OS was poorer for women with estrogen-receptor negative disease (n = 32) compared to estrogen-receptor positive (n = 60) (log-rank p = 0.031), but PFS was not significantly different (p = 0.11). RR was 59 % among the 74 patients with measurable disease. Grade 3 and 4 adverse events were 48 and 16 %, respectively. Grade 4 neutropenia was 12 % and grade 3/4 febrile neutropenia was 3 %. Common grade 3/4 nonhematologic toxicities were fatigue (14 %), pneumonitis (10 %), and dyspnea (9 %). The combination of docetaxel and vinorelbine is an active first-line chemotherapy in HER-2 nonoverexpressing, metastatic breast cancer. This combination is associated with significant hematologic and nonhematologic toxicity. The safety profile and expense of the filgrastim limit recommendations for routine use.     

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.     

Reduction in rate of node metastases with breast screening: consistency of association with tumor size

Population screening has brought about changes in both the incidence and mortality rates of patients with breast cancer. Large numbers of small screen-detected tumors have inspired discussions about overdiagnosis based on potential biological differences between screen-detected and symptomatic cancers. In the current systematic review, we analyzed the relation and the interaction of tumor size and nodal status in correlation with screening. Smaller tumors were more frequently screen detected (pT1 78.5 %) than symptomatic (pT1 61.7 %, p < 0.001), with a RR of 1.6 (95 % CI 1.4–1.8, n = 41,209). In the screened population, pT1 tumors were also more frequent (68.5 vs 49.9 %, n = 51,171, p < 0.001). Positive lymph nodes were less frequent in screen-detected tumors (26.8 vs 46.3 %, n = 43,705, p < 0.001) as well as in screened populations as a whole (24.1 vs 44.9 %, n = 49,581, p < 0.001). The relation between size and nodal status was not different between the screen-detected and the symptomatic tumors [pT2+N+ OR 2.42 (95 % CI 1.69–3.48) vs OR 2.91 (95 % CI 2.41–3.51)], suggesting that biological differences, if present, are small. In this systematic review, we confirmed both the association of screening with smaller tumor size at presentation and the consequent reduction in lymph node metastases.     

Vasohibin-1 expression detected by immunohistochemistry correlates with prognosis in non-small cell lung cancer

Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) encodes a plasma membrane protein of divalent cation channels and is expressed in keratinocytes. This study aimed to investigate CHRNA9 single-nucleotide polymorphisms (SNPs) for association with non-small cell lung cancer (NSCLC), especially squamous cell carcinoma (SCC) risk, in a Chinese population. This case–control study included 500 NSCLC patients and 500 age-matched healthy controls. CHRNA9 rs56159866, rs6819385, rs55998310, and rs182073550 SNPs were genotyped and associated for NSCLC risk by computing the odds ratios (ORs) and 95 % confidence intervals (CIs) from multivariate unconditional logistic regression analyses with adjustment for age. The frequencies of the CHRNA9 rs6819385 G allele were 16.1, 15.2, and 20.8 % in male NSCLC patients, male SCC patients, and male controls, respectively. The CHRNA9 rs6819385 A allele was associated with an increased risk of developing NSCLC (P = 0.04, OR = 1.37; 95 % CI 1.02–1.83) and SCC (P = 0.04, OR = 1.47; 95 % CI 1.01–2.13). The CHRNA9 rs6819385 A/A homozygote was associated with an increased risk of NSCLC and SCC in all patients (OR = 1.38; 95 % CI 1.06–1.79; P = 0.02, and OR = 1.61; 95 % CI 1.09–2.38; P = 0.02, respectively) and in male patients (OR = 1.57; 95 % CI 1.11–2.21; P = 0.01, and OR = 1.70; 95 % CI 1.11–2.61; P = 0.01, respectively), indicating that the CHRNA9 rs6819385 A/A homozygote had a 1.61-fold and 1.70-fold increased risk of developing lung SCC in all patients (95 % CI 1.09–2.38, P = 0.02) and in males (95 % CI 1.11–2.61, P = 0.01), respectively. The CHRNA9 rs6819385 SNP was significantly associated with an increased risk of NSCLC, especially for SCC in male patients in this Chinese population.     

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.     

Association of C-peptide and leptin with prostate cancer incidence in the Health Professionals Follow-up Study

Purpose

Hyperinsulinemia is hypothesized to influence prostate cancer risk. Thus, we evaluated the association of circulating C-peptide, which is a marker of insulin secretion, and leptin, which is secreted in response to insulin and influences insulin sensitivity, with prostate cancer risk.

Methods

We identified prostate cancer cases (n = 1,314) diagnosed a mean of 5.4 years after blood draw and matched controls (n = 1,314) in the Health Professionals Follow-up Study. Plasma C-peptide and leptin concentrations were measured by ELISA. Odds ratios (ORs) and 95 % confidence intervals (CI) were estimated taking into account the matching factors age and history of a PSA test before blood draw and further adjusting for body mass index, diabetes, and other factors.

Results

Neither C-peptide (quartile [Q]4 vs. Q1: OR 1.05, 95 % CI 0.82–1.34, p-trend = 0.95) nor leptin (Q4 vs. Q1: OR 0.85, 95 % CI 0.65–1.12, p-trend = 0.14) was associated with prostate cancer risk. Further, neither was associated with risk of advanced or lethal disease (n = 156 cases; C-peptide: Q4 vs. Q1, OR 1.18, 95 % CI 0.69–2.03, p-trend = 0.78; leptin: Q4 vs. Q1, OR 0.74, 95 % CI 0.41–1.36, p-trend = 0.34).

Conclusions

In this large prospective study, circulating C-peptide and leptin concentrations were not clearly associated with risk of prostate cancer overall or aggressive disease. Well into the PSA era, our findings do not appear to be supportive of the hypothesis that hyperinsulinemia influences risk of total or aggressive prostate cancer.     

Family history of breast cancer and local recurrence after breast-conserving therapy

The impact of a family history of breast cancer on the local recurrence (LR) risk after breast-conserving therapy (BCT) was performed within the framework of a large, multicentre matched case–control study of risk factors for LR after BCT (BORST study). Family history was assessed for 218 breast cancer patients with LR (cases) and 480 patients without LR (controls). Detailed histological tumour features were determined by review of the primary tumour. The risk of LR for patients with a positive family history was similar to or less than that of non-familial patients (unadjusted odds ratio (OR_unadj) 0.66 (95% confidence interval (CI) 0.40–1.08)). Familial patients were older than non-familial patients (P=0.07) and their tumours had a lower histological grade (P=0.07). A second primary tumour occurred significantly more often in familial patients (P=0.02). Adjustment for these factors did not essentially alter the results (OR_adj 0.71 (0.38–1.32)). Separate analyses according to age at onset (younger and older than 50 years) and time to LR/site of LR produced similar results. The sole presence of a positive family history of breast cancer does not appear to be a risk factor for local recurrence after BCT. Whilst this might be different for genetically predisposed patients, a positive family history does not appear to be a contra-indication for BCT.     

A meta-analysis of laparoscopy compared with open colorectal resection for colorectal cancer

The aim of this study was to compare the outcome of the overall complication, mortality, and recurrence rate between laparoscopic resection and open surgery for colorectal cancer. We searched the Medline, Embase, and Cochrane Library and systematically reviewed the randomized controlled trials by comparing the overall complication, mortality, and recurrence rate between laparoscopic resection and open surgery for colorectal cancer. Fifteen trials with 4,207 patients who reported long-term outcomes of the overall complication, mortality, and recurrence rate were included. The combined results of the individual trials showed no statistically significant difference in the odds ratio (OR) for overall recurrence (OR 0.92, 95% CI, 0.77–1.11, P = 0.34), local recurrence (OR 0.81, 95% CI, 0.59–1.12, P = 0.20), distant metastasis (OR 1.01, 95% CI, 0.78–1.30, P = 0.95), wound-site recurrence (OR 1.97, 95% CI, 0.77–5.02, P = 0.16), colorectal cancer-related mortality (OR 0.82, 95% CI, 0.66–1.02, P = 0.07), colon cancer-related mortality (OR 0.85, 95% CI, 0.66–1.09, P = 0.20), rectal cancer-related mortality (OR 0.76, 95% CI, 0.53–1.11, P = 0.16), and overall mortality (OR 0.87, 95% CI, 0.73–1.73, P = 0.11) between the laparoscopic surgery and open surgery groups. The overall complications in the laparoscopic surgery group were much lower than that in the open surgery group (OR 0.71, 95% CI, 0.58–0.87, P = 0.001). This meta-analysis showed that the successful laparoscopic colorectal resection for colorectal cancer was as effective as open surgery in terms of the oncological outcomes, thereby suggesting that laparoscopic surgery can be continued in patients with colorectal cancer.