Ductal carcinoma in situ or DCIS, a precursor of breast cancer, usually found during a mammogram as part of breast cancer screening, is the presence of abnormal cells inside a milk duct in the breast. While noninvasive and not life-threatening, it may progress to invasive breast cancer if left untreated and therefor requires treatment.

Historically, many women with DCIS underwent mastectomy but today the majority undergo lumpectomy. Following a lumpectomy, many women also receive radiation therapy, which approximately halves the rate of cancer recurrence in the same breast. Previous studies in breast and other cancers, however, have shown that radiation to the heart region can increase long-term risks of cardiovascular disease, so in recent years doctors have adjusted protocols to decrease exposure of the heart to radiation.

Cardiovascular risk
Past studies examining the cardiac toxicity of irradiation patients with DCIS – especial left- versus right-side – have shown an increased risk of cardiac morbidity and mortality. One study showed that among patients with left-sided breast cancer, 13.5% of patients developed a cardiovascular event compared to 7% of right-sided patients. Reviewing patients records of 129 patients with DCIS treated with breast conservation therapy from 1986 to 2002, these researchers at Division of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, found that the overall survival in their study at 8 years was 96% and the relapse-free survival was 85%. They did not find significant differences in cardiac mortality or morbidity between right- and left-sided DCIS patients treated with breast conservation therapy or BCT. However, the researchers concluded that a longer follow-up would be required.[1][2]

The study did not show differences in cardiovascular disease risks between patients who received surgery alone and those that received surgery plus radiation

Port Worthy

Now a large population-based study in The Netherlands found that women who had received radiation therapy to treat DCIS have no increased risk of cardiovascular disease compared to the general population of Dutch women, nor compared to DCIS patients treated with surgery only.[3]Understanding these results may be helpful to women who are deciding on their treatment plan. They further seem reassuring for DCIS survivors treated with radiotherapy.

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Long-term effects
This study is the first large – population based – study to evaluate long-term effects of radiotherapy for DCIS on both the incidence of cardiovascular disease and associated death rates. The results were presented during ASCO’s 2013 Breast Cancer Symposium, being held on Saturday, September 7 – Monday, September 9 at the San Francisco Marriott, San Francisco, CA.

?Doctors have been worried about late effects of breast radiation therapy, particularly cardiovascular disease. 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. This is especially important in light of the current concerns about over-treating patients diagnosed with DCIS,? noted said Naomi B. Boekel, MSc, a PhD-student at the Netherlands Cancer Institute (NKI) in Amsterdam, The Netherlands and lead author of the study ?However, studies with longer follow-up after breast radiation therapy are needed before definitive conclusions about cardiovascular disease risk can be drawn.?

Study design
Researchers collected data on 10,468 women in The Netherlands diagnosed with DCIS before the age of 75 years between 1989 and 2004. About 71% of women were treated with surgery alone (of whom 43% underwent mastectomy and the rest underwent lumpectomy) and 28% were treated with surgery and radiotherapy. The median follow-up period was 10 years and about 19% of women were followed for 15 or more years.

Risk of cardiovascular disease was compared to that of the general population of women living in The Netherlands. The results showed that five-year survivors of DCIS had a similar risk of dying due to any cause (standardized mortality ratio (SMR)=1.04 95% confidence interval (CI) 0.97-1.11), but a lower risk of dying of cardiovascular disease or CVD (SMR=0.77 95% CI 0.67-0.89). Additionally, comparisons were made between different treatment groups. After a median follow-up of 10 years, DCIS survivors had a similar risk of dying of any cause but a 30% lower risk of dying from cardiovascular disease or CVD compared to the general population of women in The Netherlands.

The scientists did not find a differences in CVD risks between patients who received surgery alone and those that received surgery plus radiation (9% of patients treated with surgery alone vs. 8% of the patients treated with surgery plus radiation were diagnosed with CVD), or between patients who received left- vs. right-sided radiotherapy (7% vs. 8% of the patients were diagnosed with CVD).

The researchers found that left- vs. right-sided radiotherapy did also not increase this risk (hazard ratio (HR)=0.93 95% CI 0.67-1.30). In a subgroup analysis of patients diagnosed between 1997 and 2005, accounting for overall history of CVD before DCIS diagnosis, the researchers did not observe a risk difference between treatment groups (left vs. right-sided radiotherapy HR=0.95 95% CI 0.69-1.30). When taking into account CVD that occurred two years prior to a diagnosis with DCIS only, however, a statistically non-significantly increased risk was seen for patients with a history of CVD (HR=1.84 95% CI 0.45-7.50).

Lower risk explained
Boekel explained that the reason why DCIS survivors had a slightly lower risk of dying from cardiovascular disease may be caused by the fact that – as it turned out – these women were more health conscious than women in the general population. This, she noted, possibly prompted these patients to undergo breast cancer screening in the first place. Another factor is that these women may have assumed a healthier lifestyle after DCIS diagnoses. Furthermore, education, socioeconomic status, or conflicting risk factors between cardiovascular disease and DCIS, such as age at menopause, may have also play a role.

General Session IV: Poster Discussion A/Abstract #58
Date: Saturday, September 7, 2013, 4:00 ? 4:20 PM PDT
Location: Yerba Buena Ballroom, Salon 8
Study Author: Naomi B. Boekel, MSc

For More information:
[1] Park CK, Li X, Starr J, Harris EE. Cardiac morbidity and mortality in women with ductal carcinoma in situ of the breast treated with breast conservation therapy. Breast J. 2011 Sep-Oct;17(5):470-6. doi: 10.1111/j.1524-4741.2011.01122.x. Epub 2011 Jul 15.[Article][PubMed]
[2] Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, Solin LJ. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006 Sep 1;24(25):4100-6. Epub 2006 Aug 14.[PubMed]
[3] Boekel NB, Schaapveld M, Gietema JA, Rutgers EJ, Versteegh MIM, Visser O, et al. Cardiovascular morbidity and mortality in patients treated for ductal carcinoma in situ of the breast. J Clin Oncol 31, 2013 (suppl 26; abstr 58) [Abstract]

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