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Originally published as JCO Early Release 10.1200/JCO.2009.22.2588 on May 26 2009 © 2009 American Society of Clinical Oncology.
Cutaneous Melanoma During Pregnancy: Is the Controversy Over?Genetic Epidemiology Unit, King's College London, St Thomas' Hospital, London, United Kingdom
Department of Biomedicine and Surgery, Faculty of Health Sciences, University of Linköping, Linköping, Sweden
Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, St James's Hospital, Leeds, United Kingdom To the Editor: We read with interest the article by Stensheim et al1 reporting the results of a survival analysis in a Norwegian cohort of 42,511 women diagnosed with cancer during the reproductive period. The effect of pregnancy or lactation at diagnosis was determined. Because the effect of pregnancy on the clinical course and prognosis of melanoma is still a subject of concern and ongoing debate among clinicians, it is important to put the results of this well-performed cohort study1 in context for melanoma patients by reviewing the pivotal published evidence. We also wish to compare the results of this study with the results of the large Swedish cohort study,2 in which we looked at the effect of pregnancy at diagnosis on survival in patients with melanoma, published in Journal of Clinical Oncology in 2004. The results of the Norwegian study reported by Stensheim et al1 are consistent with those of previous reports, indicating that cutaneous melanoma is the most common malignancy encountered during pregnancy3,4 (accounting for 31% of all malignancies diagnosed). This study did not examine the influence of pregnancy on risk of melanoma in the women of the cohort. Although various epidemiologic studies evaluating the relationship between pregnancy and melanoma risk have produced conflicting results in the past, current evidence suggests that pregnancy does not increase risk of melanoma.5 Moreover, it seems that there is reduced risk of melanoma associated with parity in women, which may reflect reduced opportunity for sunbathing rather than the effect of pregnancy-induced hormonal changes, because risk for men is also reduced with birth of children.6 The advantage of the Norwegian1 and Swedish2 studies is their long follow-up (median follow-up, 11.9 years in the Norwegian study v 11.6 years in the Swedish study), which is important in evaluating the natural history of melanoma. Both studies reported identical incidence of cutaneous melanoma during pregnancy among women age 16 to 49 years (around 3.3%). The median age of women diagnosed with melanoma during pregnancy was identical in both studies (29 years), and the median ages in the nonpregnant groups were similar (39 years in the Norwegian study v 36 years in the Swedish study). Overall survival at age 60 years was similar in both studies; in the Norwegian study, it was 72% in the pregnant group and 75% in the nonpregnant group, and in the Swedish study, reported survival rates were 77% and 74%, respectively.
Stensheim et al1 reported an increased risk of cause-specific death in women diagnosed with melanoma during pregnancy (hazard ratio [HR], 1.52; 95% CI, 1.01 to 2.31; P = .047). The published results of the Swedish study2 did not include risk of cause-specific death. However, we have calculated cause-specific survival to compare it with the results of the Norwegian study. Kaplan-Meier survival curves are presented in Figure 1. The log-rank test did not detect a statistically significant difference in cause-specific survival in women with melanoma diagnosed during pregnancy when compared with women with melanoma diagnosed while not pregnant (
The influence of pregnancy on survival in melanoma has long been a controversial issue. However, the results of two large population-based studies2,7 have shown that pregnancy does not adversely influence survival in women with melanoma. Findings from this Norwegian study by Stensheim et al1 are clearly consistent with results of the published Swedish2 and Californian7 studies, and thus they clearly support the view that survival in pregnant women with melanoma is not worse than survival in nonpregnant women with melanoma, when corrected for prognostic factors such as Breslow thickness and tumor site. As underlined by Stensheim et al, there is no evidence that pregnancy-induced hormonal changes have an adverse effect on survival in women diagnosed with melanoma during pregnancy. In conclusion, we should feel confident that the published results of large-scale population-based studies have additionally elucidated the effect of pregnancy on survival in women with melanoma. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Stensheim H, Møller B, van Dijk T, et al: Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: A registry-based cohort study. J Clin Oncol 27:45–51, 2009. 2. Lens MB, Rosdahl I, Ahlbom A, et al: Effect of pregnancy on survival in women with cutaneous malignant melanoma. J Clin Oncol 22:4369–4375, 2004. 3. Lens M, Bataille V: Melanoma in relation to reproductive and hormonal factors in women: Current review on controversial issues. Cancer Causes Control 19:437–442, 2008.[CrossRef][Medline] 4. Matthiasen L, Berg G: Malignant melanoma is the most common type of cancer occurring in pregnancy. Läkartidningen 86:2845–2848, 1989.[Medline] 5. Karagas MR, Zens MS, Stukel TA, et al: Pregnancy history and incidence of melanoma in women: A pooled analysis. Cancer Causes Control 17:11–19, 2006.[CrossRef][Medline] 6. Kaae J, Andersen A, Boyd HA, et al: Reproductive history and cutaneous malignant melanoma: A comparison between women and men. Am J Epidemiol 165:1265–1270, 2007. 7. O'Meara AT, Cress R, Xing G, et al: Malignant melanoma in pregnancy. A population-based evaluation. Cancer 103:1217–1226, 2005.[CrossRef][Medline]
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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2 = 0.11; P = .738). Our results from the multivariable analysis using the Cox proportional hazards regression model failed to show an increased risk for pregnant women diagnosed with melanoma (HR, 1.17; 95% CI, 0.59 to 2.32; P = .658). Although the results of the Norwegian study revealed an increased risk of cause-specific death in pregnant women with melanoma, only borderline significance was shown. Furthermore, it is not clear how Stensheim et al built the multivariable Cox proportional hazards regression model. It seems that the multivariable analysis did not include data on Breslow thickness (available for only 55% of women in pregnant group) and melanoma body site. In fact, when adjusted for body site, results failed to demonstrate a significant difference in cause-specific death between pregnant and nonpregnant women (HR, 1.45; 95% CI, 0.96 to 2.21). A lack of complete data on Breslow thickness is a limiting factor in survival analyses, because Breslow thickness represents a crucial prognostic factor in patients with cutaneous melanoma. To produce more reliable results, inclusion of all other histologic prognostic variables is important in building a multivariable model, which can control for several confounding variables simultaneously. 
