education clinical care research birth rates among female cancer survivors: a population-based study...
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Education
Clinical Care
Research
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
Clinical Care
Research
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