Fertility preservation for people with cancer
Pregnancy and risk of cancer recurrence
Clinical Question One
Does pregnancy increase the risk or delay the diagnosis of cancer recurrence for women with a history of breast cancer?
A meta-analysis of 14 studies performed by Azim et al. observed that women who became pregnant following breast cancer diagnosis had a 41% reduced risk of death compared to survivors who did not become pregnant [PRR: 0.59 (95% confidence interval (CI): 0.50–0.70)]. This difference was seen irrespective of the type of the study and particularly in women with history of node-negative disease. In a subgroup analysis, the outcome of women with history of breast cancer who became pregnant was compared to breast cancer patients who did not get pregnant and were known to be free of relapse. In this analysis, there was no significant difference in survival between the groups [PRR: 0.85; 95% CI: 0.53–1.35].
A more recent meta-analysis by Hartmen et al. found that women who become pregnant after a breast cancer diagnosis have a significantly reduced risk of death compared to those who do not become pregnant [pHR 0.63; 95 % CI 0.51-0.79]. Additional analysis to account for the "healthy mother effect" generated similar results [pHR 0.65; 95 % CI 0.52-0.81].
A case-control study of over 1,000 breast cancer patients performed by Lambertini et al. did not identify pregnancy as a risk factor for disease recurrence. At a median follow-up of 7.2 years after pregnancy, no difference in disease-free survival was observed between pregnant and non-pregnant patients with ER-positive (HR = 0.94, 95% CI = 0.70 to 1.26, P = 0.68) or ER-negative (HR = 0.75, 95% CI = 0.53 to 1.06, P = 0.10) disease. This supported results from an earlier study of over 10,000 breast cancer survivors that found that women who had a full-term pregnancy after breast cancer treatment had a reduced risk of dying (relative risk: 0.73; 95% confidence interval: 0.54-0.99) compared to other women with breast cancer.
A more recent study of over 30,000 Korean women treated for breast cancer has further strengthened the evidence. Lee et al. found that women who became pregnant after breast cancer did not have a different risk of recurrence (hazard ratio [HR], 0.503; 95% confidence interval [CI], 0.434 to 0.584) and death (HR, 0.520; 95% CI, 0.397 to 0.681), compared with those who did not become pregnant after breast cancer treatment.
Evidence Summary One
|Pregnancy in women with low-risk breast cancer does not increase the risk of breast cancer recurrence or death.||III-3||, , , , |
|Women treated for low-risk breast cancer should be informed that pregnancy does not appear to increase the risk of disease recurrence or mortality.||C|
Clinical Question Two
Does pregnancy increase the risk or delay the diagnosis of cancer recurrence for women with a history of cancer?
Pregnancy induces wide-ranging physiological changes, and all body systems are in some way affected by the pregnant state. These include changes to haematological parameters and the immune and hormonal environments. Additionally, there is the possibility that pregnancy may delay the diagnosis of cancer recurrence, either because of clinical reluctance to perform investigations that would permit diagnosis (or the optimal investigations are unsafe or impractical in pregnancy), or because the symptoms and signs suggestive of recurrence might be ascribed to or masked by pregnancy.
There is limited literature on the impact of pregnancy on disease recurrence for cancers other than in breast cancer. Byrom et al. published a meta-analysis on the impact of pregnancy on melanoma mortality and recurrence and found no significant effect of subsequent pregnancy on melanoma mortality after 11 to 20 years of follow-up (pooled HR, 0.81; 95% CI 0.60–1.09) and no significant differences in melanoma recurrence. The most recent of the papers found that women who had post-cancer pregnancies the risk of cause-specific death was significantly decreased and pregnancy status after diagnosis of melanoma was not a significant predictor of survival (hazard ratio for death in women who had pregnancy subsequent to the diagnosis of melanoma was 0.58; 95% CI, 0.32 to 1.05).
A cohort study by Weibull et al. investigated whether there is an association between pregnancy and relapse in women with Hodgkin lymphoma. The adjusted HR for the comparison of the pregnancy-associated relapse rate to the non–pregnancy-associated relapse rate was 0.29 (95% CI, 0.04 to 2.18). The expected number of relapses in women with a recent pregnancy, given that they would experience the same relapse rate as that of women without a recent pregnancy, was 3.76; the observed-to-expected ratio was 0.27 (95% exact CI, 0.01 to 1.51). A smaller study found no evidence that pregnancy increases the recurrence rate among women in remission from Hodgkin lymphoma.
Evidence Summary Two
|Pregnancy appears to have no effect on recurrence rates or disease survival in women with a history of melanoma or Hodgkin lymphoma.||III-3||, , , , |
|Women treated for lymphoma and melanoma should be informed that pregnancy does not appear to increase the risk of disease recurrence. Women with a history of other cancers should seek specialist advice regarding the potential impact of pregnancy on cancer recurrence.||C|
- Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, et al. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer 2011 Jan;47(1):74-83 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20943370.
- Hartman EK, Eslick GD. The prognosis of women diagnosed with breast cancer before, during and after pregnancy: a meta-analysis. Breast Cancer Res Treat 2016 Nov;160(2):347-360 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27683280.
- Lambertini M, Kroman N, Ameye L, Cordoba O, Pinto A, Benedetti G, et al. Long-term Safety of Pregnancy Following Breast Cancer According to Estrogen Receptor Status. J Natl Cancer Inst 2018 Apr 1;110(4):426-429 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29087485.
- Kroman N, Jensen MB, Wohlfahrt J, Ejlertsen B, Danish Breast Cancer Cooperative Group. Pregnancy after treatment of breast cancer--a population-based study on behalf of Danish Breast Cancer Cooperative Group. Acta Oncol 2008;47(4):545-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18465320.
- Lee MH, Kim YA, Hong JH, Jung SY, Lee S, Kong SY, et al. Outcomes of Pregnancy after Breast Cancer in Korean Women: A Large Cohort Study. Cancer Res Treat 2019 Sep 3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/31476846.
- Byrom L, Olsen CM, Knight L, Khosrotehrani K, Green AC. Does pregnancy after a diagnosis of melanoma affect prognosis? Systematic review and meta-analysis. Dermatol Surg 2015 Aug;41(8):875-82 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26177116.
- Stensheim H, Møller B, van Dijk T, Fosså SD. Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a registry-based cohort study. J Clin Oncol 2009 Jan 1;27(1):45-51 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19029418.
- Lens MB, Rosdahl I, Ahlbom A, Farahmand BY, Synnerstad I, Boeryd B, et al. Effect of pregnancy on survival in women with cutaneous malignant melanoma. J Clin Oncol 2004 Nov 1;22(21):4369-75 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15514378.
- Weibull CE, Eloranta S, Smedby KE, Björkholm M, Kristinsson SY, Johansson AL, et al. Pregnancy and the Risk of Relapse in Patients Diagnosed With Hodgkin Lymphoma. J Clin Oncol 2016 Feb 1;34(4):337-44 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26668344.
- Gaudio F, Nardelli C, Masciandaro P, Perrone T, Laddaga FE, Curci P, et al. Pregnancy rate and outcome of pregnancies in long-term survivors of Hodgkin's lymphoma. Ann Hematol 2019 Aug;98(8):1947-1952 Available from: http://www.ncbi.nlm.nih.gov/pubmed/30997537.
Body of Evidence
|Citation||Level of Evidence||Quality of Evidence||Size of Effect||Number of Patients||Relevance of Evidence|
|Anderson RA, Brewster DH, Wood R, Nowell S, Fischbacher C, Kelsey TW, et al. The impact of cancer on subsequent chance of pregnancy: a population-based analysis. Hum Reprod 2018 Jul 1;33(7):1281-1290 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29912328.||III-3||Low||N/A||23,201||N/A|
|Armuand G, Skoog-Svanberg A, Bladh M, Sydsjö G. Reproductive Patterns Among Childhood and Adolescent Cancer Survivors in Sweden: A Population-Based Matched-Cohort Study. J Clin Oncol 2017 May 10;35(14):1577-1583 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28350518.||III-3||Low||N/A||1,206||N/A|
|Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2013 Aug;14(9):873-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23856401.||III-3||High||N/A||4,897||N/A|
|Baxter NN, Sutradhar R, DelGuidice ME, Forbes S, Paszat LF, Wilton AS, et al. A population-based study of rates of childbirth in recurrence-free female young adult survivors of non-gynecologic malignancies. BMC Cancer 2013 Jan 23;13:30 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23343211.||III-3||Medium||N/A||N/A||N/A|
|Byrne J, Mulvihill JJ, Myers MH, Connelly RR, Naughton MD, Krauss MR, et al. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer. N Engl J Med 1987 Nov 19;317(21):1315-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3683460.||III-3||Medium||N/A||N/A||N/A|
|Chow EJ, Stratton KL, Leisenring WM, Oeffinger KC, Sklar CA, Donaldson SS, et al. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2016 May;17(5):567-76 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27020005.||III-3||Medium||N/A||10,938||N/A|
|Dillon KE, Sammel MD, Ginsberg JP, Lechtenberg L, Prewitt M, Gracia CR. Pregnancy after cancer: results from a prospective cohort study of cancer survivors. Pediatr Blood Cancer 2013 Dec;60(12):2001-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24038829.||II||Medium||N/A||200||N/A|
|Gerstl B, Sullivan E, Ives A, Saunders C, Wand H, Anazodo A. Pregnancy Outcomes After a Breast Cancer Diagnosis: A Systematic Review and Meta-analysis. Clin Breast Cancer 2018 Feb;18(1):e79-e88 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28797766.||III-3||High||N/A||N/A||N/A|
|Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 2009 Jun 1;27(16):2677-85 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19364965.||III-3||Medium||N/A||6,590||N/A|
|Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2010 Jan 10;28(2):332-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19949008.||III-3||Medium||N/A||7,516||N/A|
|Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003 Feb 15;21(4):716-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12586811.||III-3||Medium||N/A||8,405||N/A|
|Hartman M, Liu J, Czene K, Miao H, Chia KS, Salim A, et al. Birth rates among female cancer survivors: a population-based cohort study in Sweden. Cancer 2013 May 15;119(10):1892-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23436251.||III-3||Low||N/A||3,907,708||N/A|
|Lee HM, Kim BW, Park S, Park S, Lee JE, Choi YJ, et al. Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study. Breast Cancer Res Treat 2019 Jul;176(2):419-427 Available from: http://www.ncbi.nlm.nih.gov/pubmed/31020470.||III-3||High||N/A||18,000||N/A|
|Magelssen H, Melve KK, Skjaerven R, Fosså SD. Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood. Hum Reprod 2008 Jan;23(1):178-86 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18024486.||III-3||Medium||N/A||N/A||N/A|
|Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, et al. Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009 Aug;18(8):2239-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19661083.||III-3||Low||N/A||10,483||N/A|
|Tang SW, Liu J, Juay L, Czene K, Miao H, Salim A, et al. Birth rates among male cancer survivors and mortality rates among their offspring: a population-based study from Sweden. BMC Cancer 2016 Mar 8;16:196 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26955945.||III-3||Low||N/A||3,145,998||N/A|
|Wasilewski-Masker K, Seidel KD, Leisenring W, Mertens AC, Shnorhavorian M, Ritenour CW, et al. Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study. J Cancer Surviv 2014 Sep;8(3):437-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24711092.||III-3||Medium||N/A||1,622||N/A|
|Winther JF, Boice JD Jr, Svendsen AL, Frederiksen K, Stovall M, Olsen JH. Spontaneous abortion in a Danish population-based cohort of childhood cancer survivors. J Clin Oncol 2008 Sep 10;26(26):4340-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18779621.||III-3||High||N/A||1,688||N/A|