Monday, April 21, 2014

Delayed Childbearing and Breast Cancer Risks: A Population Level Study of Women in the United States

A Brief Background 

    For decades we have known that the act of bearing children can have a protective affect against the development of breast cancer in women. This was discussed in 1968 by Joseph Fraumeni Jr. who studied cancer mortality rates of catholic nuns in the United States between 1950 and 1954. He concluded that nulliparity (never bearing children) and the associated lack of hormonal changes that come with pregnancy had a significant impact on the development of cancers, especially cancers of reproductive organs such as the breast. This study sparked a huge debate over whether or not to allow nuns to use oral contraceptives–against the views of the catholic church (2). With this in mind we can look deeper into the conclusions drawn by Joseph Fraumeni concerning child birth and breast cancer. I have chosen to focus on whether the age at which a woman has her first child can affect her risk of developing breast cancer. Currently, women who have children before the age of 24 are thought to have a reduced risk of developing breast cancer. The best way to look at this data is to focus on a small subset of people and look at the data we have available, after-all it is these type of trends and patters that give rise to new forms of diagnostics and treatments.

Looking at the Data: Table 1 
Source: CDC NCHS data brief

     This table shows the average age at which women gave birth to their first child in the United States between the years of 1970 and 2006. I have included a red line to denote 24 years of age; any point below the line suggests that the women experience a protective effect against breast cancer, and any point above not provide the woman with that protection.  Why are women having their first child later in life? This is most likely due to the fact that women in the last few decades have become more independent; by attending college and holding professional jobs it is possible for many women to start families when they are stable in terms of finances and career paths, whereas this may have not been possible in earlier years. If this theory is correct we should see a higher incidence of cancer as the years progress. One important caveat of the data presented is that the women who have had children in 1970 should not experience the protective effects until later in life due to the fact that the onset of breast cancer should presents later; however the general trend of cancer incidence should increase in a similar manner to that of the average age at first childbirth.

Graph 1:  SEER Database 
     This graph is the age adjusted incidence of cancer between the years of 1975 and 2010 in the United States. I have decided to look 10 years into the future when making connections between the age of women who bear children and the related incidence of cancer. While this could be done much better using better surveillance techniques, this will give us a general idea of the protective effects of pregnancy on the development of early onset breast cancer. It is clear that the women of 1970 had the lowest incidence of cancer as represented in 1980. As you follow the general increase in mother's age, we also see a general increase in breast cancer diagnoses. The overall incidence of breast cancer increased by about 16% across the nearly 40 years studied. 


Source: Generated from SEER Database (plot of only adjusted data)
Cancer sites include invasive cases only unless otherwise noted. Rates are per 100,000 and are age-adjusted to the 2000 US Std Population (19 age groups - Census P25-1130). Regression lines are calculated using the Joinpoint Regression Program Version 4.1.0, April 2014, National Cancer Institute. Incidence source: SEER 9 areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta


What can we conclude?
     We have come a long way since connecting the dots between nulliparious nuns and an increased risk of breast cancer.  This small set of datum suggests that there is a correlation between the age of a mother when she has her first child and her risk of developing breast cancer. The number of diagnoses in women has increased from 72 to about 84 in 100,000 women(~16%), but there are many other environmental factors that can increase a woman's risk. If it is hard to accept the idea that we can draw an arbitrary cutoff line at which pregnancy is beneficial, we can at least conclude that as the age of mother's increase the risk of developing breast cancer also increases. But what does this mean for breast cancer studies in general? While this information is interesting, it is hardly feasible to advise women to have children before a designated age to reduce their risk of breast cancer—after all not every woman develops breast cancer due to her individual family planning options. Additionally, this data is not nearly supported enough to stop women from having children after the cutoff of 24. Therefore, in terms of diagnostics, this information on its own is essentially useless. I chose to focus on this topic not because I believe that women should all have children at very young ages, but because if we can determine how and why pregnancy provides protection we will better understand what "goes wrong" within a cell and how to counteract it rather than chasing symptoms.   Many sources claim that pregnancy hormones are the critical components of protection, but if this is the case why should age matter? Is a woman only capable of producing the necessary cancer preventing hormones at a specific age? If this is true perhaps hormones should be considered in treatment plans.  On the other side of the debate, and one that Megan and I will delve deeper into  as our project progresses, is the molecular mechanisms that give rise to this protective effect. Our preliminary sources have found connections in the stem cell differentiation events that occur during the first pregnancy of a woman's life that leads to new stem cells that are less susceptible to mutations and DNA damage. Pregnancy clearly plays a larger role in women's health than simply as a means of passing on genetic traits. As we learn more about the hormonal and molecular changes that occur within a woman's body we will be better prepared to treat diseases such as breast cancer. 

Cited Sources
  1. Fraumeni JF Jr, Lloyd JW, Smith EM, et al. “Cancer mortality among nuns: role of marital status in etiology of neoplastic disease in women”. J Natl Cancer Inst 1969;42:455–468. 
  2. Whitaker, Lucy. “The plight of nuns: hazards of nulliparity”J Fam Plann Reprod Health Care (2012) 38 (2): 116 
  3. Russo, Jose “The Protective Role of Pregnancy in Breast Cancer”Breast Cancer Research 2005, 7:131-142
  4. Matthews, TJ, and Brady Hamilton. "About United States Cancer Statistics (USCS)." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 07 Jan. 2014. Web. 23 Apr. 2014. Serach Term: Delayed Childbearing: More Women Are Having Their First Child Later in Life
  5. "Surveillance, Epidemiology, and End Results ProgramTurning Cancer Data Into Discovery." Surveillance, Epidemiology, and End Results Program. N.p., n.d. Web. 23 Apr. 2014. Look only at in breast cancer in females, age adjusted incidence in women under 65 years of age.