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Birth rates among female cancer survivors: a population-based studyPresented by Jenny Liu

04 NOV 2011

Saw Swee Hock School of Public Health

Early diagnosis ↑ Effectiveness of cancer treatment

↑ women of fertile age → long term cancer

survivors

↑ age at first birthAdvances in fertility

preservation techniques

Introduction

>75% women diagnosed with cancer < 45 years, survive at

least 5 years

One in every 1000 adults is a survivor of

childhood cancer

Hewitt M WS, Simone JV, eds: Childhood cancer survivorship: improving care and quality of life. 2003

Will I live to see my child

grow up?

Will I pass the cancer to

my child?

Will I be fit enough to

have a baby?

Will the treatment affect the

health of my baby?

Can I afford the

expenses?

Methods

• Sweden Multi-Generation Register

(Personal records, register of births)• Sweden Cancer Register• Cause of Death Register• Migration Register• Population censuses 1960, 1970, 1980 and 1990.

(socioeconomic status)

Multi-Generation Register - Sweden

Year 19321960 2002

20032004

Birth year of Index persons

Cause of Death register

Cancer register

Observation Period

1958

Statistical methods

• Relative birth rates were expressed as Standardized Birth Ratio (SBR)

• Multivariate Poisson regression modeling were applied using only data from cancer survivors and expressed as birth rate ratios (BRRs).

Log (Event / risk) = α + β1X1 + β2X2 + β3X3 +…+ βkXk

Expected no. of births in cancer population

No. of births in General Population

Person years in General PopulationX

Person Years in Cancer Population

SBR

Observed no. of births in cancer population

Expected no. of births in cancer population

=

=

Table 1 Women diagnosed with cancer in Sweden 1960-2001 with information on subsequent birth(s)

 Number of

women with previous cancer

Number of women with

births

Total number of births

Proportion of women who gave birth after cancer

diagnosis

Overall 42691 4932 8080 11.6%

Parity status at diagnosis        

Nulliparous 13437 3276 5982 24.4%

Parous 29254 1656 2098 5.7%

Cancer site        

Breast 12139 124 214 1.0%

Reproductive (minus ovary) 6493 358 648 5.5%

Melanoma Skin 4637 31 52 0.7%

Table 2 Standardized Birth Ratios of women with a history of cancer.

Overall 0.74 (0.73-0.76)

Parity status at diagnosis  

Nulliparous 0.87 (0.85-0.89)

Parous 0.52 (0.50-0.55)

Cancer site  

Reproductive (minus ovary) 0.33 (0.30-0.36)

Breast 0.55 (0.50-0.60)

Ovary 0.57 (0.51-0.62)

Brain & eye 0.67 (0.63-0.71)

Hematopoietic 0.68 (0.63-0.73)

Bone 0.83 (0.77-0.89)

Others 0.84 (0.74-0.93)

Digestive tract 0.91 (0.84-0.98)

Thyroid 0.99 (0.94-1.04)

Head & neck 1.00 (0.87-1.14)

Thoracic 1.03 (0.77-1.33)

Melanoma Skin 1.05 (1.00-1.11)

SBR same as background population

Standardized Birth Ratios of women with a history of cancer by cancer site and parity status at diagnosis

SBR for nulliparous women

SBR for parous women

Table 4 Poisson Regression Model of relative likelihood of giving birth for women with a history of cancer

Parity status at diagnosis Adjusted Birth Rate Ratio* (95% CI)

Nulliparous 1.00

Parous 0.64 (0.61-0.68)

Age at diagnosis  

0-12 years old (Childhood) 1.00

13-18 years old (Adolescence) 1.26 (1.12-1.41)

19-45 years old (Adulthood) 1.50 (1.31-1.72)

Time since diagnosis  

1-5 yrs 1.00

6-10 yrs 1.06 (0.99-1.12)

11-20 yrs 1.16 (1.05-1.28)

21-35 yrs 1.31 (1.09-1.58)

*Adjusted for cancer site, period of diagnosis, calendar period, attained age and socio-economic status.

Findings• Female cancer survivors were 26% less likely to give birth compared

to the background population.

• Following a cancer diagnosis, women with the lowest fertility were those with previous child birth, cancer of the reproductive organs and breast, those diagnosed during childhood and recent diagnosis.

• Large differences in Standardized birth ratios by parity status at diagnosis are suggestive of differential willingness among cancer survivors to pursue a/another child.

• Identifying women at increased risk of infertility post-diagnosis will allow for possible family planning and still give women the choice of parenthood after a cancer diagnosis.

Acknowlegements

Saw Swee Hock School of Public Health, National University of Singapore

• Prof Mikael Hartman

• Prof Chia Kee Seng

• Dr Agus Salim

• Miss Miao Hui

• Funding: NMRC/1180/2008 and NUS Start-up Fund DPRT

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden

• Prof Kamila Czene

• Swedish Initiative for research on Microdata in the Social and Medical Sciences (SIMSAM), grant number 80748301

Department of Radiology, University Medical Center Utrecht, The Netherlands

• Prof Helena M Verkooijen

Education

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Thank you for your attention!

Extra slides

Target Population

Age

20021932 1961Year of Birth

Deceased/emigrated 1932-1960

10

20

30

40

50

60

70Target population = All index persons

Born 1932 onwards

Resident 1961 onwardsTarget

population

Female aged 16-45

Mothers of index persons

Table 1 Women diagnosed with cancer in Sweden 1960-2001 with information on subsequent birth(s)

  ICD7 codesNumber of women

with previous cancer

Number of women with

births

Total number of

births

Proportion of women who gave birth after

cancer diagnosis

Overall - 42691 4932 8080 11.6%Parity status at diagnosis          Nulliparous - 13437 3276 5982 24.4%Parous - 29254 1656 2098 5.7%Cancer site          Breast 170.0-170.9 12139 124 214 1.0%

Reproductive (minus ovary) 171.0-174.9; 176.0-176.9 6493 358 648 5.5%

Skin 190.0-190.9 4637 31 52 0.7%Brain & eye 192.0-193.9 3797 342 470 9.0%Thyroid 194.0-195.9 3682 307 464 8.3%Hematopoietic 201.0-208.9 2566 268 448 10.4%Ovary 175.0-175.9 2553 958 1521 37.5%Digestive tract 150.0-158.9 2439 639 1084 26.2%Bone 196.0-200.9 2109 885 1430 42.0%

Others180.0-181.9; 191.0-191.9;

209.0-209.91226 376 677 30.7%

Head & neck 140.0-148.9; 160.0-161.9 674 465 776 69.0%Thoracic 162.0-164.9 376 179 296 47.6%Age at diagnosis          0-12 (Childhood) - 1521 440 867 28.9%13-18 (Adolescence) - 1618 638 1282 39.4%19-45 (Adult) - 39552 3854 5931 9.7%Year of diagnosis          1958-1968 - 2333 841 1560 36.0%1969-1979 - 9219 1292 2243 14.0%1980-1990 - 15443 1664 2777 10.8%1991-2001 - 15696 1135 1500 7.2%Socio-economic Status          Blue Collar Workers - 14800 1635 2687 11.0%White Collar Workers - 18198 2236 3727 12.3%Self-employed - 1134 99 174 8.7%Farmers - 344 31 52 9.0%Unclassified - 8215 931 1440 11.3%

Table 2 Standardized Birth Ratios of women with a history of cancer.

  SBR

Overall 0.74 (0.73-0.76)

Parity status at diagnosis  

Nulliparous 0.87 (0.85-0.89)

Parous 0.52 (0.50-0.55)

Age at diagnosis  

0-12 0.73 (0.68-0.78)

13-18 0.82 (0.78-0.87)

19-45 0.73 (0.71-0.75)

Year of diagnosis  

1958-1968 0.78 (0.74-0.82)

1969-1979 0.73 (0.70-0.76)

1980-1990 0.74 (0.72-0.77)

1991-2001 0.73 (0.69-0.77)

Time since diagnosis  

1-5 yrs 0.71 (0.68-0.73)

6-10 yrs 0.79 (0.75-0.82)

11-20 yrs 0.80 (0.76-0.84)

21-35 yrs 0.73 (0.67-0.81)

Attained Age  <22 0.77 (0.69-0.85)22-27 0.78 (0.75-0.82)28-33 0.77 (0.75-0.80)34-39 0.68 (0.65-0.71)>39 0.58 (0.52-0.65)

Socio-economic Status  

Blue Collar Workers 0.68 (0.65-0.71)

White Collar Workers 0.82 (0.79-0.84)

Self-employed 0.74 (0.64-0.86)

Farmers 0.87 (0.65-1.12)

Unclassified 0.70 (0.66-0.74)

Table 2 Standardized Birth Ratios of women with a history of cancer by parity status at diagnosis and cancer site.

Cancer site Overall Parous Nulliparous

Reproductive (minus ovary) 0.33 (0.30-0.36) 0.21 (0.18-0.24) 0.53 (0.47-0.60)

Breast 0.55 (0.50-0.60) 0.38 (0.33-0.43) 0.94 (0.82-1.06)

Ovary 0.57 (0.51-0.62) 0.48 (0.40-0.57) 0.60 (0.54-0.67)

Brain & eye 0.67 (0.63-0.71) 0.60 (0.52-0.68) 0.69 (0.64-0.74)

Hematopoietic 0.68 (0.63-0.73) 0.39 (0.32-0.46) 0.77 (0.71-0.83)

Bone 0.83 (0.77-0.89) 0.56 (0.46-0.66) 0.92 (0.84-0.99)

Others 0.84 (0.74-0.93) 0.76 (0.61-0.94) 0.87 (0.76-0.99)

Digestive tract 0.91 (0.84-0.98) 0.61 (0.50-0.72) 1.02 (0.93-1.11)

Thyroid 0.99 (0.94-1.04) 0.83 (0.76-0.91) 1.08 (1.01-1.15)

Head & neck 1.00 (0.87-1.14) 0.79 (0.60-1.00) 1.12 (0.95-1.30)

Thoracic 1.03 (0.77-1.33) 0.73 (0.43-1.12) 1.28 (0.89-1.73)

Skin 1.05 (1.00-1.11) 0.82 (0.74-0.89) 1.19 (1.12-1.26)

Birth Rate Ratios Unadjusted BRR (95% CI) p-value Adjusted BRR* (95% CI) p-valueParity status before diagnosis        Nulliparous 1.00   1.00  Parous 0.40 (0.38-0.42) <.0001 0.64 (0.61-0.68) <.0001Cancer site        Melanoma Skin 1.00   1.00  Breast 0.24 (0.21-0.26) <.0001 0.52 (0.47-0.58) <.0001Reproductive (minus ovary) 0.37 (0.33-0.41) <.0001 0.42 (0.38-0.47) 0.2233Brain & Eye 0.79 (0.73-0.85) <.0001 0.71 (0.65-0.77) <.0001Ovary 0.83 (0.74-0.92) 0.0004 0.70 (0.63-0.78) <.0001Hematopoietic 0.87 (0.80-0.95) 0.0022 0.74 (0.68-0.81) <.0001Thyroid 0.98 (0.91-1.05) 0.5671 0.96 (0.89-1.03) <.0001Bone 1.14 (1.04-1.25) 0.0037 0.97 (0.89-1.07) <.0001Others 1.18 (1.04-1.34) 0.0082 1.09 (0.96-1.24) 0.2962Digestive tract 1.23 (1.12-1.35) <.0001 1.06 (0.97-1.16) 0.5877Head & Neck 1.66 (1.44-1.91) <.0001 1.41 (1.22-1.64) <.0001Thoracic 2.96 (2.25-3.91) <.0001 2.04 (1.54-2.70) 0.1794Age at diagnosis        0-12 1.00   1.00  13-18 1.31 (1.20-1.42) <.0001 1.26 (1.12-1.41) 0.000119-45 0.88 (0.82-0.94) 0.0003 1.50 (1.31-1.72) <.0001Year of diagnosis        1958-1968 1.00   1.00  1969-1979 0.68 (0.64-0.72) <.0001 0.84 (0.77-0.92) 0.00011980-1990 0.61 (0.57-0.65) <.0001 0.78 (0.68-0.88) <.00011991-2001 0.56 (0.52-0.60) <.0001 0.72 (0.62-0.85) <.0001Time since diagnosis        1-5 yrs 1.00   1.00  6-10 yrs 1.35 (1.28-1.42) <.0001 1.06 (0.99-1.12) 0.078911-20 yrs 1.51 (1.42-1.60) <.0001 1.16 (1.05-1.28) 0.002321-35 yrs 1.86 (1.68-2.05) <.0001 1.31 (1.09-1.58) 0.0041Calendar period        1960-1969 1.00   1.00  1970-1979 0.67 (0.60-0.74) <.0001 0.86 (0.76-0.96) 0.00931980-1989 0.50 (0.46-0.55) <.0001 0.90 (0.78-1.04) 0.15241990-2002 0.61 (0.55-0.66) <.0001 1.09 (0.92-1.29) 0.3289Attained age        16-18 1.00   1.00  19-21 5.83 (4.19-8.10) <.0001 5.35 (3.85-7.45) <.000122-24 10.98 (8.00-15.09) <.0001 9.26 (6.72-12.78) <.000125-27 13.94 (10.18-19.10) <.0001 11.66 (8.44-16.10) <.000128-30 13.86 (10.13-18.96) <.0001 12.12 (8.76-16.78) <.000131-33 10.13 (7.40-13.86) <.0001 9.65 (6.95-13.41) <.000134-36 6.48 (4.73-8.88) <.0001 6.67 (4.78-9.31) <.000137-39 3.88 (2.82-5.33) <.0001 4.41 (3.14-6.19) <.000140-42 2.05 (1.47-2.86) <.0001 2.63 (1.85-3.75) <.000143-45 0.77 (0.51-1.17) 0.2237 1.26 (0.81-1.96) 0.3016Socio-economic Status        Blue Collar Workers 1.00   1.00  White Collar Workers 0.98 (0.93-1.03) 0.4423 1.00 (0.95-1.05) 0.9788Self-employed 2.60 (2.23-3.03) <.0001 2.05 (1.76-2.39) <.0001Farmers 3.67 (2.79-4.82) <.0001 2.16 (1.63-2.86) <.0001Unclassified 1.08 (1.01-1.15) 0.0164 1.01 (0.94-1.08) 0.7787

Standardized Birth Ratio in women with a history of cancer with increasing age by age at diagnosis

Standardized Birth Ratios of women with a history of cancer with increasing age by

parity status at diagnosis