Devera Pine

Women with ductal carcinoma in situ (DCIS) treated with radiation therapy had no increased risk of cardiovascular disease (CVD) compared with women in the general population or women with DCIS treated with surgery, according to results of a study in The Netherlands. The study was presented at the 2013 Breast Cancer Symposium, held September 7-9 in San Francisco, California.

&ldquo;Doctors have been worried about late effects of breast radiation therapy, particularly cardiovascular disease,&rdquo; said Naomi B. Boekel, MSc, the study&rsquo;s lead author and a PhD student at The Netherlands Cancer Institute in Amsterdam. &ldquo;Our findings suggest that routine radiation therapy for women with DCIS does not appear to increase the risk of developing cardiovascular disease later in life.&rdquo;

The researchers collected data on 10,468 women in The Netherlands diagnosed with DCIS before the age 75 years between 1989 and 2004. About 71% of the women were treated with surgery alone (43% had a mastectomy and the rest underwent lumpectomy) and 28% were treated with surgery and radiotherapy. The median follow-up was 10 years; 19% of the women were followed for 15 years or more. The study compared the risk of CVD in women treated with radiotherapy with that of the general population of Dutch women and to different treatment groups of women with DCIS.

Compared with the general population, women with DCIS had a similar risk of dying from any cause (standardized mortality ratio [SMR] = 1.04; 95% CI, 0.97-1.11) and a 30% lower risk of dying of CVD (SMR = 0.77; 95% CI, 0.67-0.89). No difference was found in the risk of CVD in women treated with radiotherapy versus surgery alone (8% of patients treated with surgery plus radiation were diagnosed with CVD vs 9% treated with surgery alone). Likewise, no significant differences in the risk of CVD were observed in patients who received left-side radiotherapy (7%) versus right-side (8%; hazard ratio [HR] = 0.93; 95% CI, 0.67-1.30).

The findings are important in light of current concerns about overtreating patients with DCIS, said Boekel. Radiation therapy following lumpectomy for DCIS approximately halves the rate of cancer recurrence in the same breast. However, previous studies in breast and other cancers have shown that radiation to the heart region can increase the long-term risk of CVD, and in recent years, radiation therapy protocols have been adjusted to decrease exposure of the heart to radiation.

The slightly lower risk of dying from CVD in women with DCIS might be the result of those women being more health conscious than the general population, so that they underwent breast cancer screening or adopted a healthier lifestyle after DCIS diagnosis, Boekel said. In addition, factors such as education, socioeconomic status, and conflicting risk factors between CVD and DCIS (eg, age at menopause) may also play a role. &ldquo;Studies with longer follow-up after breast radiation therapy are needed before definitive conclusions about cardiovascular disease risk can be drawn,&rdquo; she said.

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Women with DCIS treated with radiation therapy had no increased risk of cardiovascular disease compared with women in the general population or women with DCIS treated with surgery.

Radiation Therapy for DCIS Does Not Increase Risk of Cardiovascular Disease

Although a variety of biomarkers have been shown to correlate with survival in men with prostate cancer, the use of biomarkers in the management of these patients may be dependent upon the clinical state and the class of drug evaluated. Speaking at the 6th Annual Interdisciplinary Prostate Cancer Congress, held in New York City on March 16, Daniel P. Petrylak, MD, director of the Genitourinary Oncology Program at Yale Cancer Center in New Haven, Connecticut, reviewed the evidence for biomarkers to date. &ldquo;There is nothing at this point that has fallen out as absolutely prognostic or predictive in an individual situation,&rdquo; he said.

One area of interest is the prognostic value of promoter methylation of genes associated with various parameters of prostate cancer progression.

was the only epigenetic event significantly associated with a worse disease-free or disease-specific survival. There was a trend toward worse outcome in patients treated with androgen- deprivation therapy (ADT) who had

hypermethylation was associated with a shorter time to biochemical relapse (disease-free survival) in patients treated with prostatectomy (

=.043), but not in patients treated with external-beam radiation therapy or ADT.

Okegawa et al assessed whether circulating tumor cells (CTCs) with tumorrelated methylated DNA could be used to predict survival in patients with hormone- refractory prostate cancer.

The researchers analyzed blood samples from 76 patients; CTC evaluations occurred 3.5 to 78.5 months after the initial diagnosis. Serum DNA methylation status was assessed for

Use of biomarkers in the management of prostate cancer may be dependent upon the clinical state and the class of drug evaluated

Approximately half of patients do not have detectable CTC levels by current detection methods

Research on biomarkers should be an element in phase III trials

A total of 47 patients (62%) had 5 or more CTCs and a median overall survival (OS) of 12 months compared with 26 months for patients with fewer than 5 CTCs (P<.001). The presence of 5 or more CTCs was significantly correlated with the detection of 1 or more methylated loci (P <.001). The median OS for patients with methylated DNA was 12 months versus 48 months or more for patients without methylated DNA (

Posttreatment CTC levels were shown to predict OS in a study of 231 patients with progressive CRPC

; data from the study led to FDA approval of the Cell- Search assay. However, in his talk, Petrylak said that although CTCs are useful for predicting treatment response or survival with cytotoxic and hormonal therapies, about half of patients do not have detectable CTC levels by current detection methods. More-sensitive CTC detection techniques are needed, he said.

gene fusion, which is present in approximately half of newly diagnosed prostate cancer cases, has also been investigated as a biomarker, though the clinicopathologic impact of the fusion is not clear, Petrylak said. Different subtypes of

have been detected, and the Edel subtype may represent a more lethal genotype, susceptible to higher recurrence, more likely to evolve to CRPC and to progress to metastasis.

as a predictive biomarker for sensitivity to abiraterone acetate; however, a phase II trial found that the fusion has a limited role in this area.

In summary, Petrylak said, although a variety of biomarkers correlate with survival, none are &ldquo;ready for prime time.&rdquo; However, he said, research on biomarkers should be an element in all subsequent phase III trials.

Roupret M, Hupertan V, Catto JW, et al. Promoter hypermethylation in circulating blood cells identifies prostate cancer progression.

Henrique R, Ribeiro FR, Fonseca D, et al. High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients.

Okegawa T, Nutahara K, Higashihara E. Association of circulating tumor cells with tumor-related methylated DNA in patients with hormone-refractory prostate cancer.

de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer.

Mehra R, Tomlins SA, Yu J, et al. Characterization of TMPRSS2-ETS gene aberrations in androgen- independent metastatic prostate cancer.

Danila DC, Anand A, Sung CC, et al. TMPRSS2- ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate.

Although biomarkers have been shown to correlate with survival in prostate cancer, the use of biomarkers in the management of these patients may be dependent upon the clinical state and the class of drug evaluated.

Devera Pine | Authors

Articles

Radiation Therapy for DCIS Does Not Increase Risk of Cardiovascular Disease

Biomarkers Still Needed in Prostate Cancer