The American Society of Clinical Oncology’s 2011 annual meeting was held June 3-7 in Chicago. The features below highlight some of the news emerging from the meeting.
» SNPs Linked to Neuropathy in Breast Cancer
» PSA Predicts Long-Term Prostate Cancer Risk
» Validity of Concurrent HPV Testing & Cervical Cytology
» The Effects of Ovarian Cancer Screening on Mortality
» Smoking, Alcohol, & Physical Activity: The Effect on Cancer Risk
The Particulars: Neuropathy is one of the most common toxicities experienced by patients on taxane therapy. The resulting pain can be severe, function-limiting, and sometimes irreversible. Advanced age, diabetes, and type, dose, and schedule of taxane have been established as predictors for increased risk, but no biomarkers have been identified to help predict patients who are at greatest risk.
Data Breakdown: A genome-wide association study was performed on 2,204 patients under-going paclitaxel therapy with early stage breast cancer with the purpose of identifying single nucleotide polymorphisms (SNPs) that could be associated with a first grade 2 to 4 neuropathy. In the investigation, 613 patients experienced grade 2 to grade 4 neuropathy. Age (12.9% increase per 10 years) and African-American race were identified as significant clinical predictors. Residing in two genes (RWDD3 and TECTA), six SNPs with minor allele frequency greater than 5% were associated with time to neuropathy. The likelihood of neuropathy at 15 months was associated with a missense SNP in RWDD3 (27% for patients with homozygous wild-type, 40% for heterozygous, and 60% for homozygous variant) and a TECTA SNP (29% for homozygous wild-type, 32% for heterozygous, and 57% for homozygous variant).
Take Home Pearl: Several SNPs appear to be associated with time to neuropathy among patients with breast cancer who are undergoing paclitaxel therapy.
PSA Predicts Long-Term Prostate Cancer Risk [back to top]
The Particulars: PSA testing remains a controversial tool in prostate cancer diagnosis because many men need to be screened before deaths can be prevented. Few data are available to help form the basis of current prostate cancer screening recommendations.
Data Breakdown: PSA levels were analyzed in 12,090 men primarily between the ages of 44 and 50. Of these, 4,999 provided repeat samples 6 years later, and 1,167 men provided blood at age 60. Evidence of prostate cancer death or metastasis was ascertained in 252 men. Death and metastasis risks were strongly associated with PSA levels obtained up to 30 years prior. In men aged 44 to 50, 44% of cancer deaths occurred in those with PSA levels greater than 1.6 ng/ml. Although a median-level PSA in men aged 44 to 50 did not rule out metastases or death risks, it did have an effect on older men. Researchers found that 28.0%, 18.0%, and 0.5% of metastases occurred in men with a median PSA level at ages 44 to 50, 51 to 55, and 60 and older, respectively.
Take Home Pearls: Nearly half of prostate cancer deaths appeared to be preventable with intense surveillance, especially among men aged 44 to 50 with the highest PSA levels. A PSA test between ages 51 and 55 and again at age 60 appears to sufficiently capture risk of prostate cancer metastases or death 10 or more years in advance.
Validity of Concurrent HPV Testing & Cervical Cytology [back to top]
The Particulars: As an alternative to cytology alone, concurrent HPV testing and cervical cytology appears to hold promise for women aged 30 and older. However, few routine clinical practice data are available on co-testing, particularly for women who test negative for HPV and have normal cytology (HPV-/Pap-).
Data Breakdown: In a study involving 331,818 women enrolled in co-testing with HPV screening and cervical cytology, researchers estimated 5-year cumulative incidence of cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+). In HPV- and HPV-/Pap- women, 5-year cancer risks were similarly low when compared with Pap- women. Cytology alone was less able to clearly separate women with high/low 5-year CIN3+ risk than was HPV testing alone. For HPV+ women, 5-year CIN3+ risk was greatly increased with abnormal cytology, but not for HPV- women. Of HPV+ women, 73% had no cytologic abnormality. Of all women, those who were HPV+ experienced 34% of CIN3+, 29% of all cancers, and 63% of all adenocarcinomas.
Take Home Pearls: HPV-based screening with concurrent HPV testing and cervical cytology appears to promote earlier identification of women at high risk for cervical cancer, especially adenocarcinoma. It also gave strong reassurance against cervical cancer over 5 years for HPV-.
The Effects of Ovarian Cancer Screening on Mortality [back to top]
The Particulars: Ovarian cancer is one of the top five causes of cancer death in American women. Significantly improved survival has been expected in women diagnosed with early stage disease when compared with those with advanced disease. The effect of screening on mortality for early disease using cancer antigen 125 (CA-125) and transvaginal ultrasound (TVU) remains unknown.
Data Breakdown: In a study of 78,000 women aged 55 to 74, patients were randomized into two groups that received either usual care or an intervention that involved annual screening with CA-125 testing for 6 years and TVU for 4 years. After 13 years follow-up, 212 women in the intervention group and 176 in the usual care group were diagnosed with ovarian cancer. In the intervention arm, 118 women died, compared with 100 in the usual care arm. Among 3,285 women who underwent surgery after a false positive exam, 166 experienced at least one serious complication.
Take Home Pearls: Screening women in the general population with simultaneous CA-125 and TVU does not appear to reduce ovarian cancer mortality. False positive screening tests appear to result in both.
Smoking, Alcohol, & Physical Activity: The Effect on Cancer Risk [back to top]
The Particulars: In the Breast Cancer Pre-vention Trial, the risk of breast cancer was reduced by 50% for those who received tamoxifen when compared with those who received placebo. However, few studies have compared tamoxifen to placebo for other common cancers and have taken self-reported cigarette smoking, alcohol use, and physical activity into consideration.
Data Breakdown: In a clinical investigation, tamoxifen (20 mg/day) or a placebo was randomly administered to 11,064 women who were considered at high risk for breast cancer. At a median of 8.7 years potential follow-up, invasive breast and lung cancers were predicted by baseline smoking. Endometrial cancer was predicted by low physical activity. A decreased colon cancer risk was seen in those who consumed zero or one alcoholic drinks per day when compared with those who abstained from drinking. The authors noted that consumption of one or more drinks per day was not associated with increased risk of any cancer.
Take Home Pearls: Smoking and physical activity appear to be linked to increased cancer risk in women at high risk for breast cancer. How-ever, alcohol use does not appear to increase this risk.