The association of menstrual and reproductive factors with upper gastrointestinal tract cancers in the NIH‐AARP cohort

BACKGROUND:

In most populations, incidence rates of upper gastrointestinal (UGI) tract cancers (head and neck, esophagus, and stomach) are higher among men than among women. Established risk factors do not appear to explain these differences, suggesting a possible role for sex hormones.

METHODS:

201,506 women of the NIH‐AARP Diet and Health cohort completed a questionnaire in 1995‐1996. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models.

RESULTS:

During follow‐up through 2003, 162 incident adenocarcinomas (ACs; esophagus, N = 25, and stomach, N = 137) and 353 incident squamous cell carcinomas (SCCs; head and neck, n = 297, and esophagus, N = 56) occurred. Among examined exposures, older age at menopause was associated inversely with SCC (P_trend across categories = .013) but not AC (P_trend = .501). Use of menopausal hormone therapy (MHT) was significantly associated with lower risk of SCC (hazard ratio [HR] = 0.77, 0.62‐0.96) and nonsignificantly associated with lower risk of AC (HR = 0.81, 0.59‐1.12). A subset (N = 127,386) of the cohort completed a more detailed MHT questionnaire a year after baseline. In 74,372 women with intact uteri, ever use of estrogen‐progestin MHT conferred 0.47 (0.30‐0.75) times the risk for SCC and 0.52 (0.26‐1.07) times the risk for ACC. In 51,515 women with a hysterectomy before baseline, we found no associations between use of estrogen MHT and AC or SCC.

CONCLUSIONS:

Higher estrogen and progesterone levels may be related inversely to UGI cancers and in this way help explain lower incidence rates in women compared with men. Cancer 2010. © 2010 American Cancer Society.     

Prostate cancer‐specific mortality and the extent of therapy in healthy elderly men with high‐risk prostate cancer

BACKGROUND:

The risk of prostate cancer‐specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external‐beam radiation to the prostate and seminal vesicles, and androgen‐suppression therapy (CMT) in this population.

METHODS:

The study cohort comprised 764 men aged ≥65 years with high‐risk prostate cancer (T3 or T4N0M0, prostate‐specific antigen >20 ng/mL, and/or Gleason score 8‐10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM.

RESULTS:

The median patient age was 73 years (interquartile range, 70‐77 years). After a median follow‐up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12‐0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017).

CONCLUSIONS:

Elderly men who had high‐risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high‐risk prostate cancer. Cancer 2010. © 2010 American Cancer Society.     

P63 differentiates subtypes of nonsmall cell carcinomas of lung in cytologic samples

BACKGROUND:

Bevacizumab in combination with carboplatin and paclitaxel improves overall response and survival in patients with advanced or recurrent nonsmall cell lung carcinoma. However, this drug is not recommended in patients with squamous cell carcinoma or neoplasms with a dominant squamous component. Therefore, identification of squamous cell differentiation has therapeutic implications. In many instances, cytology is the diagnostic tool of choice; however, routine cytomorphology is limited in classification of nonsmall cell carcinomas into squamous and nonsquamous subtypes. The aim of this study was to identify the value of p63 immunocytochemical analysis in this distinction.

METHODS:

Review of cytology records identified 51 consecutive pulmonary specimens (16 fine needle aspiration samples, 15 washes, 12 brushes, and 8 lavages) with the diagnosis of nonsmall cell lung carcinoma (9 carcinomas with squamous differentiation and 42 carcinomas without squamous differentiation). Histologically, they all proved to be nonsmall cell carcinomas, 26 with squamous differentiation and 25 without squamous differentiation. p63 immunocytochemical stain was performed on archival alcohol‐fixed Papanicolaou‐stained cytology slides using standard immunocytochemical methods.

RESULTS:

Twenty‐three (88 %) of the 26 histologically proven squamous cell carcinomas were positive for p63 on cytologic smears. By using p63 immunocytochemistry, the authors detected 14 carcinomas with squamous differentiation not identified by cytomorphology. Smears from all histologically proven carcinomas with squamous differentiation were positive for p63. Sensitivity of cytology for the detection of nonsmall cell carcinoma of lung with squamous differentiation increased from 35% to 88% using p63 immunocytochemistry (P = .001; McNemar test). The squamous component in 4 carcinomas was detected only in cytologic and not in corresponding histologic samples when subsequent p63 immunostaining was performed.

CONCLUSIONS:

The authors concluded that p63 is a useful marker for the detection of nonsmall cell carcinomas of lung with squamous differentiation when used in cytologic pulmonary samples. p63 immunocytochemistry significantly increases the sensitivity for the identification of lung neoplasms with squamous differentiation from 35% to 88% (P = .001). Therefore, p63 immunocytochemistry may be used in pulmonary cytologic samples of nonsmall cell carcinomas to identify squamous differentiation and to improve therapeutic selection of patients with lung cancer. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Candida and dysbacteriosis: A cytologic,population‐based study of 100,605 asymptomatic women concerning cervical carcinogenesis

BACKGROUND.

The objective of this study was to investigate whether the presence of vaginal Candida or dysbacteriosis predisposes women to an increased susceptibility for (pre)neoplasia over time.

METHODS.

A retrospective, longitudinal, cohort study was performed and was conducted in a population of 100,605 women, each of whom had 2 smears taken over a period of 12 years as part of the Dutch Cervical Screening Program. From these women, a cohort of 1439 women with Candida and a cohort of 5302 women with dysbacteriosis were selected as 2 separate study groups. The control cohort consisted of women who had completely normal cervical smears (n = 87,903 women). These groups were followed retrospectively over time. The odds ratios (OR) for squamous abnormalities in the follow‐up smear for the women in these 3 cohorts were established.

RESULTS.

The dysbacteriotic cohort was significantly more likely to have low‐grade squamous intraepithelial lesions (LSIL) and high‐grade squamous intraepithelial lesions (HSIL+) in their follow‐up smear (OR, 1.85; 95% confidence interval [95% CI], 1.28–2.67 and OR, 2.00; 95% CI, 1.31–3.05, respectively) compared with women in the control group. In contrast, the Candida cohort had no significantly increased or decreased risk of developing SIL. The equivocal diagnosis ‘atypical squamous cells of undetermined significance’ was rendered significantly more often in the follow‐up smear of both study cohorts (Candida cohort: OR, 1.42; 95% CI, 1.03–1.95; dysbacteriotic cohort: OR, 1.44; 95% CI, 1.22–1.71).

CONCLUSIONS.

The results from this study indicated that the presence of Candida vaginalis was not associated with an increased risk for SIL over time. In contrast, women with dysbacteriosis had a significantly increased risk of developing (pre)neoplastic changes. These findings should be taken into account in further research concerning predisposing factors for cervical carcinogenesis. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

Modifying effect of MDM4 variants on risk of HPV16-associated squamous cell carcinoma of oropharynx

BACKGROUND:

The p53 pathway plays a critical role in maintaining genomic stability and preventing tumor formation. Given the roles of both MDM4 and HPV16 E6 oncoproteins in inhibition of p53 activity, we tested the hypothesis that MDM4 polymorphisms are associated with the risk of HPV16‐associated squamous cell carcinoma of head and neck (SCCHN).

METHODS:

Genotyping was conducted on 3 tagging single nucleotide polymorphisms (rs11801299 G>A, rs10900598 G>T, and rs1380576 C>G) in MDM4, and serology was used to determine HPV 16 exposure in 380 cases and 335 cancer‐free controls that were frequency‐matched by age, sex, smoking, and drinking status.

RESULTS:

None of 3 MDM4 polymorphisms alone was significantly associated with risk of overall SCCHN. With further analysis stratified by HPV16 serology and tumor site, we found that each polymorphism individually modified the risk of HPV16‐associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly pronounced in never smokers and never drinkers.

CONCLUSION:

The risk of HPV16‐associated SCCOP could be modified by MDM4 polymorphisms. Large and prospective studies are needed to validate our findings. Cancer 2011;. © 2011 American Cancer Society.     

Late age at first full term birth is strongly associated with lobular breast cancer

BACKGROUND:

Late age at first full‐term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades.

METHODS:

The purpose of this population‐based case‐control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal‐lobular breast cancer diagnosis in association with AFB and nulliparity.

RESULTS:

AFB ≥30 years was associated with a 2.4‐fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9‐2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2‐1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3‐2.2) than for ductal (OR, 1.2; 95% CI, 1.1‐1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer.

CONCLUSIONS:

Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer. Cancer 2011. © 2010 American Cancer Society.     

Immunohistochemical analysis of CYP2A13 in various types of human lung cancers

Human CYP2A13, which is expressed in the respiratory tract, is the most efficient enzyme for the metabolic activation of tobacco‐specific nitrosamines such as 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). The relevance of CYP2A13 in carcinogenicity and toxicity in the respiratory tract has been suggested, but the expression of CYP2A13 protein in lung cancer tissues remains to be determined. We first prepared a mouse monoclonal antibody against human CYP2A13. The antibody showed no cross reactivity with the other CYP isoforms including CYP2A6. Using the specific antibody, we performed immunohistochemical analysis for human lung carcinomas. In adenocarcinomas (n = 15), all specimens were positive for the staining and five samples showed strong staining. In squamous cell carcinomas (n = 15) and large cell carcinomas (n = 15), each 14 samples were positive for the staining and two and three samples showed strong staining, respectively. In small cell carcinoma samples (n = 15), eight samples were negative for the staining and five samples showed weak or moderate staining. In conclusion, we first found that the expression of CYP2A13 was markedly increased in non‐small cell lung carcinomas. The high expression might be associated with the tumor development and progression in non‐small cell lung carcinomas. (Cancer Sci 2010; 101: 1024–1028)     

Impact of postoperative prostate‐specific antigen disease recurrence and the use of salvage therapy on the risk of death

BACKGROUND:

This report evaluated whether biochemical recurrence (BCR) as a time‐dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

METHODS:

This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow‐up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT.

RESULTS:

After a median follow‐up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow‐up after prostate‐specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8‐16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004‐1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15‐2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40‐0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37‐0.84 [P = .005]) after BCR.

CONCLUSIONS:

The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.     

Examining stage IIB survival in a population‐based cohort of patients with colorectal cancer

BACKGROUND:

In Nova Scotia, Canada, a previous study of colorectal cancer (CRC) cases diagnosed between January 1, 2001, and December 31, 2005, found that patients with stage IIB CRC had similar 5‐year overall survival (OS) to those with stage IIIC cancer. This study sought to examine factors contributing to the observed stage IIB outcome, specifically nodal harvest, receipt of chemotherapy, and use of a new coding system to derive stage.

METHODS:

The provincial cancer registry identified all CRC cases diagnosed during the study period and staged this cohort using the Collaborative Stage (CS) Data Collection System. All patients with stage II and III cancer in the cohort were examined. Kaplan‐Meier (KM) survival curves compared 5‐year OS for patients with stage IIB cancer based on the factors of interest, and compared patients with stage IIB cancer to those with stage IIA and III cancer.

RESULTS:

OS for patients with stage IIB cancer (n = 187) was 44.7%, and differed depending on adequacy of nodal harvest (P = .005) and whether pathological or clinical/mixed evidence was used to derive stage (P = .013). Pathologically‐staged patients with stage IIB cancer who had adequate nodal harvest had marginally improved OS compared to pathologically‐staged patients who had inadequate nodal harvest (P = .07), and improved survival compared to patients with clinical/mixed stage (P = .004). Pathologically‐staged patients with stage IIB cancer with adequate nodal harvest demonstrated similar 5‐year OS to those with stage IIA and III cancer (P = .52 and P = .25, respectively). Cox proportional hazards models supported these findings.

CONCLUSIONS:

The inclusion of clinical/mixed evidence into staging classification and, perhaps to a lesser extent, the adequacy of nodal harvest appear to contribute to the observed worse survival for patients with stage IIB versus stage III cancer. Cancer 2012. © 2012 American Cancer Society.     

Pulmonary tuberculosis increases the risk of lung cancer: a population-based cohort study

BACKGROUND:

The possible effect of pulmonary tuberculosis (TB) on subsequent lung cancer development has been suspected, but the evidence remains inconsistent. The purpose of this study was to perform a nationwide population‐based cohort study to investigate the risk of lung cancer after pulmonary TB infection.

METHODS:

This nationwide population‐based cohort study was based on data obtained from the Taiwan National Health Insurance Database. In total, 5657 TB patients and 23,984 controls matched for age and sex were recruited for the study from 1997 to 2008.

RESULTS:

The incidence rate of lung cancer (269 of 100,000 person‐years) was significantly higher in the pulmonary TB patients than that in controls (153 of 100,000 person‐years) (incidence rate ratio [IRR], 1.76; 95% confidence interval [CI], 1.33‐2.32; P < .001). Compared with the controls, the IRRs of lung cancer in the TB cohort were 1.98 at 2 to 4 years, 1.42 at 5 to 7 years, and 1.59 at 8 to 12 years after TB infections. The multivariate Cox proportional hazards model revealed pulmonary TB infections (hazard ratio [HR], 1.64; 95% CI, 1.24‐2.15; P < .001) and chronic obstructive pulmonary disease (HR, 1.09; 95% CI, 1.03‐1.14; P = .002) to be independent risk factors for lung cancer.

CONCLUSIONS:

Pulmonary infection with TB is associated with an increased risk of lung cancer. Cancer 2011. © 2010 American Cancer Society.     

Outcomes after adjuvant chemotherapy in the treatment of high-risk urothelial carcinoma of the upper urinary tract (UUT-UC): results from a large multicenter collaborative study

BACKGROUND:

Urothelial carcinoma of the upper urinary tract (UUT‐UC) was a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. High‐risk patients had poor outcomes. Because of the rarity of these tumors, randomized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable. Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high‐risk, postsurgical UUT‐UC patients.

METHODS:

Using a multi‐institutional, international retrospective database, identified were 627 patients with high risk UUT‐UCs (pT3N0, pT4N0 and/or N+ and/or M+) who underwent surgical removal. Only patients who received adjuvant chemotherapy were included.

RESULTS:

Overall, 140 patients (22.6%) with a median age of 67 years were included. The median follow‐up was 22.5 months. The 5‐year, overall survival for the entire cohort was 43%, the 5‐year recurrence‐free survival was 54%, and metastasis‐free survival was 53% at 5 years. Positive surgical margins were an independent prognostic factor for recurrence (P = .06), cancer‐specific mortality (P = .05), and overall mortality (P = .02) of any cause. Adjuvant chemotherapy was not linked with overall or cancer‐specific survival in patients with high risk disease (adjuvant chemotherapy [n = 140] vs no treatment [n = 487]) (P >.5).

CONCLUSIONS:

Adjuvant postoperative chemotherapy did not offer any significant benefit to overall survival in our population. Additional data were necessary, and studies enrolling patients at high risk in clinical trials investigating neoadjuvant chemotherapy in conjunction with chemotherapy should have been highly encouraged. Cancer 2011;. © 2011 American Cancer Society.     

The use of anticoagulants improves biochemical control of localized prostate cancer treated with radiotherapy

BACKGROUND:

Substantial experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, although the limited data from clinical trials have been inconsistent. The potential antineoplastic effect of ACs was investigated in patients who received radiotherapy for localized prostate cancer.

METHODS:

The study cohort consisted of 662 patients with adenocarcinoma of the prostate who received radiotherapy (RT) with curative intent. Among those 622 men, 243 (37%) were receiving ACs (warfarin, clopidogrel, and/or aspirin). All patients received external‐beam RT, permanent seed implantation, or a combination of both. Prostate‐specific antigen (PSA) values were monitored for biochemical control of disease.

RESULTS:

At a median follow‐up of 49 months, the biochemical control rate at 4‐years was significantly better in patients who received ACs at 91% compared with 78% in patients who did not receive ACs (P = .0002). The distant metastasis rate at 4 years also was reduced in the AC group compared with the non‐AC group (1% vs 5%; P = .0248). In subgroup analysis, the improvement in biochemical control was significant only for patients with high‐risk disease. Along with Gleason score, T classification, and initial PSA, the use of AC therapy was associated independently with improved biochemical control in multivariate analysis.

CONCLUSIONS:

AC therapy was associated with an improvement in biochemical control in patients with prostate cancer who received RT with curative intent. The effect was most prominent in patients who had high‐risk disease. Cancer 2010. © 2010 American Cancer Society.     

Examination of laryngoesophageal dysfunction-free survival as an endpoint in nonsurgical treatment of squamous cell carcinomas of the larynx and hypopharynx

BACKGROUND:

A recently published consensus guideline suggested a new endpoint for clinical trials involving cancer of the larynx and hypopharynx: laryngoesophageal dysfunction‐free survival (LEDFS). The authors of this report examined LEDFS in the context of definitive radiotherapy alone (RT) or with concurrent chemoradiotherapy (CRT).

METHODS:

Patients with a stage III to IVB squamous cell carcinomas of the larynx or hypopharynx who received definitive radiotherapy were included. Consensus guidelines also suggested analysis of the following: tumor classification, lymph node status, pretreatment tracheotomy, pretreatment swallowing dysfunction, and subsite. LEDFS was assessed using Kaplan‐Meier survival analyses.

RESULTS:

Eighty‐five patients (73.9%) received CRT, and 30 patients (26.1%) received RT. For the entire cohort, the 3‐year LEDFS rate was 28.9%. CRT was associated with an improved LEDFS at 3 years (32.2% vs 20%; P = .02). Pretreatment dysphagia (P = .06) and N2 or N3 lymph node status (P = .09) demonstrated a trend toward poorer LEDFS, but patients who had T4 tumors had an LEDFS similar to that of patients who had T2 and T3 tumors.

CONCLUSIONS:

LEDFS was superior in patients who received CRT compared with patients who received RT alone. T4 status was not associated with a worse LEDFS. Cancer 2011. © 2011 American Cancer Society.     

A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus

BACKGROUND:

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have activity in solid tumors. The authors evaluated an oral EGFR TKI, erlotinib, in patients with previously treated esophageal cancer.

METHODS:

Thirty patients with measurable, metastatic cancer of the esophageal and gastroesophageal junction received 150 mg erlotinib daily. EGFR‐negative tumors (6 patients; 20%) and EGFR‐over expressing tumors (24 patients; 80%) were treated. Most patients were men (70%) with adenocarcinoma (57%) and had received previous chemotherapy (97%).

RESULTS:

Two partial responses were observe d in the EGFR‐positive cohort (2 of 24 patients; 8%), and no responses were observed in the EGFR‐negative cohort (0 of 6 patients). Reponses were limited to patients who had squamous cell carcinoma (2 of 13 patients; 15%; response duration, 5.5‐7 months). The time to tumor progression was longer in patients who had squamous cell carcinoma (3.3 months; range, 1‐24 months) compared with patients who had adenocarcinoma (1.6 months; range, 1‐6 months; P = .026). Therapy was tolerable with the expected toxicity of skin rash (grade 1‐2, 67%; grade 3, 10%).

CONCLUSIONS:

Erlotinib had limited activity in patients with esophageal cancer, and responses and some protracted stable disease were observed in those with squamous cell carcinoma. Efficacy according to EGFR status could not be assessed given the rarity of EGFR‐negative tumors. The current results indicated that further evaluation of this agent in squamous cell carcinoma is warranted. Cancer 2011. © 2010 American Cancer Society.     

Loss of MTBP expression is associated with reduced survival in a biomarker-defined subset of patients with squamous cell carcinoma of the head and neck

BACKGROUND:

Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta‐analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous.

METHODS:

The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses.

RESULTS:

Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2‐low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log‐rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12‐2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log‐rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39‐5.54) in p53 + ve/MDM2‐low patients.

CONCLUSIONS:

These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status‐dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression. Cancer 2011. © 2011 American Cancer Society.     

Amiodarone and the risk of cancer

BACKGROUND:

In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy.

METHODS:

Using the Taiwan National Health Insurance Research database, the authors conducted a population‐based cohort study. Patients who were treated with amiodarone between 1997 and 2008 were enrolled. Those with antecedent cancer were excluded. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. A multivariate Cox regression model was used to evaluate the association between cumulative defined daily doses (cDDDs) of amiodarone and cancer occurrence.

RESULTS:

The study included 6418 subjects, with a median follow‐up of 2.57 years. A total of 280 patients developed cancer. The risk of cancer increased with borderline significance (SIR, 1.12; 95% confidence interval [95% CI], 0.99‐1.26 [P = .067]). Male patients had a higher risk (SIR, 1.18; 95% CI, 1.02‐1.36 [P = .022]). The total cohort of patients and the male patients with > 180 cDDDs within the first year were found to have SIRs of 1.28 (95% CI, 1.00‐1.61; P = .046) and 1.46 (95% CI, 1.11‐1.89; P = .008), respectively. After adjustment for age, sex, and comorbidities, the hazards ratio was 1.98 (95% CI, 1.22‐3.22; P = .006) for the high tertile of cDDDs compared with the low tertile.

CONCLUSIONS:

The results of the current study indicate that amiodarone may be associated with an increased risk of incident cancer, especially in males, with a dose‐dependent effect. Cancer 2013;119:1699–1705. © 2013 American Cancer Society.     

Effectiveness of radiation for prevention of mastectomy in older breast cancer patients treated with conservative surgery

BACKGROUND:

A recent clinical trial concluded that radiation therapy (RT) does not lower the risk of mastectomy and, thus, may be omitted in older women with stage I, estrogen receptor (ER)‐positive breast cancer who undergo conservative surgery (CS). However, it is not known whether this finding applies to patients outside of clinical trials. Accordingly, we used the Surveillance, Epidemiology, and End Results‐Medicare observational cohort to determine the effect of RT on the risk of mastectomy among older women with stage I, ER‐positive breast cancer.

METHODS:

The authors identified 7403 women ages 70 to 79 years who underwent CS between 1992 and 2002. Claims were used to determine RT status and to identify women who underwent mastectomy subsequent to initial treatment. The Kaplan‐Meier method was used to estimate the risk of subsequent mastectomy, and Cox regression analysis was used to determine the effect of RT adjusted for clinical‐pathologic covariates.

RESULTS:

At a median follow‐up of 7.3 years, the risk of subsequent mastectomy within 10 years of diagnosis was 3.2% for patients who received RT versus 6.3% for patients who did not receive RT (P < .001). In adjusted analyses, RT was associated with a lower risk of mastectomy (hazard ratio, 0.33; 95% confidence interval, 0.22‐0.48; P < .001). RT provided no benefit for patients ages 75 to 79 years without high‐grade tumors who had a pathologic lymph node assessment (P = .80); however, for all other subgroups, RT was associated with an absolute reduction in risk of mastectomy that ranged from 4.3% to 9.8% at 10 years.

CONCLUSIONS:

Outside of a clinical trial, the receipt of RT after CS was associated with a greater likelihood of ultimate breast preservation for most older women with early breast cancer. Cancer 2012. © 2012 American Cancer Society.     

Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort

BACKGROUND:

There is concern that antioxidant supplement use during chemotherapy and radiation therapy may decrease treatment effects, yet the effects of such supplements on recurrence and survival are largely unknown.

METHODS:

The authors prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women in the Life After Cancer Epidemiology (LACE) cohort. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis. Baseline data were collected on antioxidant supplement use since diagnosis and other factors. BC recurrence and mortality were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using delayed entry Cox proportional hazards models. All tests of statistical significance were 2‐sided.

RESULTS:

Antioxidant supplement use after diagnosis was reported by 81% of women. Among antioxidant users, frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence (vitamin C: HR, 0.73; 95% CI, 0.55‐0.97; vitamin E: HR, 0.71; 95% CI, 0.54‐0.94); and vitamin E use was associated with a decreased risk of all‐cause mortality (HR, 0.76; 95% CI, 0.58‐1.00). Conversely, frequent use of combination carotenoids was associated with increased risk of death from BC (HR, 2.07; 95% CI, 1.21‐3.56) and all‐cause mortality (HR, 1.75; 95% CI, 1.13‐2.71).

CONCLUSIONS:

Frequent use of vitamin C and vitamin E in the period after BC diagnosis was associated with a decreased likelihood of recurrence, whereas frequent use of combination carotenoids was associated with increased mortality. The effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant. Cancer 2012. © 2011 American Cancer Society.