Abortion-breast cancer hypothesis Totally Explained

Everything about Abortion-breast Cancer Hypothesis totally explained

The abortion-breast cancer (ABC) hypothesis (supporters call it the abortion-breast cancer link) posits induced abortion increases the risk of developing breast cancer; it's a controversial subject and the current scientific consensus has concluded there's no significant association between first-trimester abortion and breast cancer risk.
The American Cancer Society concludes that presently the evidence doesn't support a causal abortion-breast cancer association, yet a causal link continues to be championed by pro-life activists like Dr. Joel Brind, Dr. Angela Lanfranchi and Karen Malec. In February 2003, the NCI responded by conducting a workshop with over 100 experts on the issue, which determined from selected evidence that it was well-established "abortion isn't associated with an increase in breast cancer risk."
Though the scientific community is largely skeptical of the hypothesis and has been rejected by some; Pro-life groups maintain they're providing legally necessary informed consent; a concern shared by conservative Congressman Dr. Dave Weldon. While early research indicated a correlation between breast cancer and abortion; the current scientific consensus has solidified with the publication of large prospective cohort studies which find no clear association between abortion and breast cancer. These studies along with all relevant research strive to remove from their results the many confounding factors, such as delayed child bearing (parity), which effect breast cancer risk apart from abortion. The abortion-breast cancer hypothesis continues to incite mostly political and some scientific debate.

Proposed mechanism

While research has shown the protective benefits of full-term pregnancy and lactation in reducing the risk of breast cancer, these benefits are only fully realized in the third trimester when differentiation of new breast growth takes place. The abortion-breast cancer hypothesis posits that if a pregnancy is aborted prior to differentiation it could have an adverse effect by creating and leaving behind more immature cells to be exposed to carcinogens and hormones over time.
Breast tissue contains many lobes (segments) and these contain lobules which are groups of breast cells. There are four types of lobules:

Type 1 has 11 ductules (immature)
Type 2 has 47 ductules (immature)
Type 3 has 80 ductules (mature, fewer hormone receptors)
Type 4 lobules are fully matured (cancer resistant) and contain breast milk

During early pregnancy type 1 lobules quickly become type 2 lobules because of changes in estrogen and progesterone levels. Maturing into type 3 and then reaching full differentiation as type 4 lobules requires an increase of human placental lactogen (hPL) which occurs in the last few months of pregnancy. According to the abortion-breast cancer hypothesis, if an abortion were to interrupt this sequence then it could leave a higher ratio of type 2 lobules than existed prior to the pregnancy. Russo and Russo have shown that mature breast cells have more time for DNA repair with longer cell cycles Bernstein et al. independently observed a reduced breast cancer risk when women were injected with hCG for weight loss or infertility treatment. Contrary to the ABC hypothesis, Michaels et al. hypothesize since hCG plays a role in cellular differentiation and may activate apoptosis, as levels of hCG increase early on in human pregnancy, "an incomplete pregnancy of short duration might impart the benefits of a full-term pregnancy and thus reduce the risk of breast cancer." After his study failed to convince the scientific community of a causal relationship, Brind co-founded the Breast Cancer Prevention Institute (BCPI) in 1999 with Dr. Angela Lanfranchi, a surgeon and pro-life advocate. In 2003, Brind was invited to the NCI workshop, where he was the only one to formally dissent.
Karen Malec, a former teacher and pro-life activist, started the Coalition on Abortion-Breast (CAB) in 1999 with help from Concerned Women for America, Research relevant to the current ABC discussion focuses on more recent large cohort studies, a few meta-analyses, many case-control studies and several early experiments with rats.

Rats

Drs. Russo & Russo from the Fox Chase Cancer Center in Philadelphia conducted a study in 1980 which examined the proposed correlation between abortion and breast cancer. Russo and Russo examined the effects of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) on the DNA labeling index (DNA-LI) in terminal end buds (TEBs), terminal ducts (TDs) and alveolar buds (ABs) of Sprague-Dawley rats in various stages of reproductive development. Russo and Russo found that rats who had interrupted pregnancies had no noticeable increase in risk for cancer.
Despite the fact that the Russos' studies found similar risk rates between virgin and pregnancy interrupted rats, their research would be used to support the contention that abortion created a greater risk of breast cancer for the next twenty years. In a Discover article sidebar entitled Humans Are Not Rats, Dr. Gil Mor, the director of reproductive immunology at the Yale University School of Medicine, disagrees with Dr. Brind on the importance of the rat studies findings. Dr. Mor emphasizes that rat studies are ideal for understanding basic processes but because rats have neither breasts nor breast cancer, people like Dr. Brind are on "wobbly" terrain.

Epidemiological studies

The majority of the results in epidemiology are calculated as a relative risk where 1.0 is no risk, but results above like 1.21 is a 21% increased risk and results below such as 0.8 is a 20% decreased risk. Relative risks are not necessarily significant. To help assess this a relative risk is followed by a confidence interval in brackets that shows the likelihood (with 95% confidence) that the relative risk is of significance. Any relative risk with a confidence interval that doesn't include a value of 1 could be considered significant. For example, the confidence intervals (0.3 - 0.9) and (1.5 - 7.8) are statistically significant, whereas the confidence intervals (0.89 - 7.34) or (0.5 - 1.1) are not. With more data the confidence interval becomes smaller; making it an indicator of the result's statistical reliability.
When a relative risk result actually becomes significant is a difficult and contentious issue. As a small result of 1.41 (1.1 - 1.6) even with a significant confidence interval (outside 1.0) may be inaccurate because of response bias, incomplete data, missed confounding factors, imprecise controls or statistical analysis. If these possible flaws are accounted for they could change the result and/or the confidence interval impacting its statistical significance.
The number of (X/Y breast cancer cases/controls) gives X as women in the study who have had induced abortion(s) and Y is women with no abortion and miscarriage history. This dataset is usually used when calculating the relative risk and provides a way to compare the size of one study to another.

Confounding factors

There are many confounding factors for breast cancer. Genetics is a major factor that affects not only a woman's initial breast cancer risk but also her hormonal sensitivity, which in turn affects her susceptibility to a long list of socioeconomic and environmental factors. As Western society has modernized environmental carcinogens, delayed child rearing, less breastfeeding, hormone replacement therapy (HRT), hormonal contraception, early menarche and obesity have increased.
   If unaccounted for these factors could obscure any individual variable. Scientific studies remove them using case-control methodology – a woman who has had an abortion (case) is matched with a very similar woman with no abortion history (control) – if this wasn't done a study could get a false positive or negative result because of another factor. Examining the ABC issue is all the more difficult because the number of women with an induced abortion history has increased along with other factors in recent decades. and higher breast cancer risk.
   All of these confounding factors have an effect, directly or indirectly, on hormones which impact breast cancer risk, but they don't significantly affect the results of ABC studies that are properly conducted and take these factors into account with case-control matching. Hormones being a key factor for cancer risk is well established. Steroidal estrogen was added to the U.S. federal carcinogen list in December 2002. The American Cancer Society (ACS) and the National Cancer Institute (NCI) note reproductive hormones can elevate breast cancer risk. In particular a Women's Health Initiative hormone replacement therapy study was cut short from an elevated breast cancer and heart risk using estrogen with progestin.
   The controversial nature of abortion may introduce response bias into interview studies, especially for studies done in decades past when abortion was less accepted.

Cohorts

Howe

The 1989 study by Dr. Holly Howe et al. at the New York State Department of Health examined young women with breast cancer in upstate New York (1,451 breast cancer cases/controls). Dr. Brind emphasizes restricting the dataset to women under 40 is a strength of the Howe study given recent legalization in 1970 and the small window of breast cancer diagnosis (1975 – 1980). The RR for women who'd given birth previous to the abortion was 0.58 (0.38 - 0.84), whereas women with no births had an RR of 1.09 (0.71 - 1.56). The confidence intervals didn't establish statistically significant associations between breast cancer and different stages of reproduction, including abortion. Overall, the RR was 0.77 (0.58 - 0.99), making for a 23% reduced risk in comparison to "contemporary Swedish population with due consideration to age." Lindefors-Harris made no adjustments for family history of breast cancer and the pill, Possibly making the protective result about parity (childbearing) rather than abortion.

Melbye

A large, highly regarded ABC study was published by Dr. Melbye et al. (1997) of the Statens Serum Institute in Copenhagen, which had 1.5 million Danish women in the study's database (1,338 breast cancer cases, no controls used).
   Drs. Brind and Chinchilli had concerns about the Melbye study database as women in the study were born from 1935 to 1978, but the computerized registry of induced abortions only started in 1973. Dr. Melbye et al. responded that if the misclassified older women had their risk underestimated, it would be expected that the younger groups would have a higher risk. The statistically adjusted data indicated this wasn't the case.
   However, the statistical adjustments made were another concern of Dr. Brind who argues that the Melbye study accidentally adjusted out induced abortion from the overall results. Instead of case-control matching Dr. Melbye el al. decided to manually remove the many confounding factors that increased over time (eg. smoking, late child bearing, etc.) and were raising breast cancer risk for younger women relative to older women (birth-cohorts). Dr. Brind believes finding exactly zero ABC risk was a consequence and red flag indicating ABC risk was removed along with the confounding factors.
   Another letter to the editor from Drs. Senghas and Dolan questioned why a statistically significant result for induced abortions done after 18 weeks gestation wasn't specifically addressed in the results section of the Melbye study abstract. Melbye et al. explained even though they found the result "interesting and in line with the hypothesis of Russo and Russo, the small number of cases of cancer in women in this category of gestational age prompted us not to overstate the finding." Another 2006 study involving 267,400 women (872/771 breast cancer cases/controls) in Shanghai found no evidence of an ABC link. In fact, this study noted that women who had an abortion were at a significantly decreased risk of uterine cancer.

Meta-analysis

Beral

In March 2004, Dr. Beral et al. published a study in The Lancet as a collaborative reanalysis on Breast cancer and abortion. This meta-analysis of 53 epidemiologic studies of 83,000 women with breast cancer undertaken in 16 countries didn't find evidence of a relationship between induced abortion and breast cancer, with a relative risk of 0.93 (0.89 - 0.96). Organizations and media outlets referenced the Beral study as the most comprehensive overview of the ABC evidence.
Dr. Brind maintains that like meta-analysis this study is subject to selection bias, which he believes is reflected in the removal of 15 published, peer-reviewed studies with positive ABC results for "unscientific reasons"; and including 28 unpublished studies that outnumber the remaining 24 peer reviewed studies. Beral refers to the Lindefors-Harris (1991) as evidence that response bias explains higher ABC risk found in interview based studies, however Brind notes in 1998 Lindefors-Harris conceded their initial conclusion may have been unsound.

Brind

Dr. Brind et al. (1996) conducted a meta-analysis of 23 epidemiologic studies. It calculated that there was on average a relative risk of 1.3 (1.2 - 1.4) increased risk of breast cancer. The meta-analysis was criticized for selection bias by using studies with widely varying results, using different types of studies and not working with the raw data from several studies, and including studies that have methodological weaknesses. Some of the ABC studies RCOG reference as evidence (pg. 77) have been heavily criticized by Brind in 2005.

Interviews

Interview (case-control) based studies have been inconsistent on the ABC link. With the small numbers involved in each individual study and the possibility that recall bias skewed the results, recent focus has switched to meta-analysis and record based studies which are typically much larger. Included are a few interview studies of note.

Daling

Dr. Janet Daling from the Fred Hutchinson Cancer Research Center headed two studies on the ABC issue looking at women in Washington state. The 1994 study (845/961 breast cancer cases/controls) results indicated an associated relative risk of 1.5 (1.2 - 1.9) among women who had given birth before having an abortion. This was reflected in higher risks for women younger than 18 or older than 30 years of age who have had abortions after 8 weeks' gestation. Their conclusion emphasized that although the evidence suggested the possibility of a correlative relationship, their findings were not consistent enough to establish one.
The second larger study Daling conducted in 1996 (1,302/1,180 breast cancer cases/controls) found that abortion was associated with a relative risk value of 1.2 (1.0 - 1.5).

Sanderson

A 2001 study (1,459/1,556 breast cancer cases/controls) conducted in Shanghai, China by Dr. Sanderson et al. from the University of South Carolina and South Carolina Cancer Center at Columbia concluded that there was no ABC link and that multiple abortions didn't put one at greater risk. Since induced abortion is common, legal, and even mandated by the government in China, the recall bias was minimized. Specifically with China’s strict population control, the vast majority of the abortions in the Chinese study were done after the first full-term pregnancy.

Response bias

Response bias occurs when women intentionally "underreport" their abortion history, meaning that they deny having an abortion or claim to have fewer abortions than they actually had. This can happen because of the personal and controversial nature of abortion, which may cause women to not want to provide full disclosure. Women in control groups are less likely to have serious illnesses, and hence have less motivation to be truthful than those trying to diagnose their problem. A review of ABC studies was conducted by Dr. Bartholomew in 1998. It concluded that if studies least susceptible to response bias are considered, they suggest there's no association between abortion and breast cancer. Chris Kahlenborn, M.D., a pro-life researcher and specialist in internal medicine, observes in his book Breast Cancer: Its Link to Abortion and the Birth Control Pill that if report bias were a significant factor in interview-based studies, then:

... thousands of other studies in medicine might now be deemed 'worthless.' Every time one had a disease or 'effect' that was caused by a controversial risk factor (for example, one of the causes), the study might be considered invalid based upon 'recall bias.'

Lindefors-Harris

The Lindefors-Harris (1991) study (317/512 breast cancer cases/controls) was the first major study to examine response and recall bias. It used the data of two independent Swedish induced abortion studies, and concluded there was a 1.5 (1.1 - 2.1) margin of error due to recall bias. However, eight women (seven cases, one control) included in this error margin apparently "overreported" their abortions, meaning the women reported having an abortion that wasn't reflected in the records. It was decided that for the purposes of the study, these women didn't have abortions. – where women were interviewed as mothers – which could have increased their tendency to underreport, given that a mother might not want to appear unfit. (12 cases and 1 control)
Dr. Rookus et al. supported their finding with an analysis of how much recall bias existed with oral contraceptive use that could be verified through records. It corroborated the bias, but Dr. Brind's et al. letter argues that it only indicated response bias between the two regions, not between case and control subjects within regions. Dr. Rookus et al. responded by noting that there was 4.5 month underreporting difference between control and case subjects in the conservative Catholic region. This was indirect evidence for a reporting bias since women's comfort levels with reporting oral contraception are theoretically higher than induced abortion. Rookus et al. also acknowledged the weakness in the Lindefors-Harris (1991) study, but emphasized that more controls (16/59 = 27.1%) than case patients (5/24 = 20.8%) underreported registered induced abortions. They concluded that asserting a causal ABC link would be a disservice to the public and to epidemiological research when "bias hasn't been ruled out convincingly." Their results were that 14.0% of cases and 14.9% controls (a difference of -0.9%) didn't accurately report their abortion history. They do note likely underreporting occurring in certain sub-groups of women; such as older women in a Newcomb study reporting abortions prior to legalization, and a predominantly Roman Catholic population in the Rookus study. although a study by Dr. Paoletti concluded there's a "suggestion of increased risk" 1.2 (0.92 - 1.56) after 3 or more pregnancy losses. Some argue that this apparent lack of effect of miscarriages on breast cancer risk is evidence against the ABC hypothesis, and some pro-choice advocates have claimed it's proof that neither early pregnancy loss nor abortion are risk factors for breast cancer. Kunz & Keller (1976) showed that when progesterone is abnormally low a miscarriage occurs 89% of the time. Advocates of the ABC hypothesis argue that, given the association of most first trimester miscarriages with low hormone levels, spontaneous abortion isn't analogous to an induced abortion.

Politicization

Public interest in an association between abortion and breast cancer coincided with the rise of the militant pro-life movement which turned to violence. However, the 1993 murder of physician David Gunn by a pro-life activist "irreparably harmed the movement". In response to the escalating violence, President Bill Clinton signed the Freedom of Access to Clinic Entrances Act (FACE) and clinic "buffer zones" were established to protect women and clinic employees. Though militant pro-life activists continued to bomb clinics and kill employees, their violence caused mainstream pro-life organizations to disavow their methods. and some feel that pro-life advocates treat ABC as simply another tactic in their campaign against abortion. In 2005, a Canadian pro-life organization put up billboards in Alberta with large pink ribbons and the statement: "Stop the Cover-Up," in reference to the abortion-breast cancer hypothesis. The Canadian Breast Cancer Foundation was concerned the billboards misrepresented the state of scientific knowledge on the subject.}}
During the late 1990s several United States congressman became involved in the ABC issue. In 1998, congressman Tom Coburn questioned a National Cancer Institute (NCI) official on why the NCI website contained out of date information on the ABC issue. Congressman Dave Weldon wrote a "Dear Colleague" letter to congress in 1999 shortly after the House debated FDA approval of the abortion drug Mifepristone; and partially as a result of John Kindley's law review on informed consent which was enclosed.
As of 2004 state law in Minnesota, Mississippi, Texas, Louisiana, and Kansas requires warning women seeking abortions about a possible breast cancer risk. Similar legislation requiring notification has also been introduced, and was pending, in 14 other states. An editor for the American Journal of Public Health expressed concern over how such legislative bills propose warnings that don't agree with established scientific findings. However, it's possible that such legally-mandated disclosure could mitigate possible future lawsuits involving informed consent from women who might contend they should have been told of the ABC hypothesis possibility prior to having an abortion.

National Cancer Institute

A report from the Committee on Oversight and Government Reform found that in November 2002, the Bush administration altered the National Cancer Institute's (NCI) website. The previous NCI analysis had concluded that while some question regarding an association between abortion and breast cancer existed prior to the mid-1990's, a number of large and well-regarded studies such as Melbye et al. (1997) had resolved the issue; and there was no link between abortion and breast cancer. The Bush administration removed this analysis and replaced it with the following:
New York Times describing it as an "egregious distortion" and a letter to the Secretary of Health and Human Services from members of Congress. Brind alleges the workshop evidence and findings were overly controlled by its organizers since Dr. Daling, who has published on the abortion-breast cancer issue, was asked to present on another topic; and preterm delivery was listed as an epidemiological "gap" even though there was preliminary evidence of a correlation with higher breast cancer risk.
Dr. Jasen notes: "A very public target of the anti-abortion movement has been the National Cancer Institute, not only for its dismissal of Daling's findings and uncritical support of Melbye's report, but also for the information supplied on its website, which potentially reaches millions of women around the world."

North Dakota lawsuit

One example of the politicization of science is the case of Kjolsrud v. MKB Management Corporation. In January of 2000 Amy Jo Kjolsrud (née Mattson), a pro-life counselor, sued the Red River Women's Clinic in Fargo, North Dakota alleging false advertising. The suit alleged the clinic was misleading women by distributing a brochure quoting a National Cancer Institute fact sheet on the ABC issue which stated:
� "Anti-abortion activists claim that having an abortion increases the risk of developing breast cancer and endangers future childbearing. None of these claims are supported by medical research or established medical organizations." (emphasis in original)

The case was originally scheduled for September 11, 2001, but was delayed as a result of the terrorist attacks. On March 25, 2002, the trial started and after four days of testimony Judge Michael McGuire ruled in favor of the clinic. In his decision he said:
Linda Rosenthal, an attorney from the Center for Reproductive Rights characterized the decision thusly: "The judge rejected the abortion-breast cancer scare tactic. This ruling should put to rest the unethical, anti-choice scare tactic of using pseudo-science to harass abortion clinics and scare women."
John Kindley, one of the lawyers representing Ms. Kjolsrud stated: "I think most citizens, whether they're pro-choice or pro-life, believe in an individual's right to self-determination. They believe people shouldn't be misled and should be told about [procedural] risks, even if there's controversy over those risks." Kindley also wrote an article published in 1998 by the Wisconsin Law Review outlining the viability of medical malpractice lawsuits based upon not informing patients considering abortion about the evidence indicating an ABC link.
The decision was appealed and on September 23, 2003, to the North Dakota Supreme Court which ruled the false advertising law shouldn't have been used by Ms. Kjolsrud. This was because she personally had suffered no injury and hence had no standing (according to North Dakota jurisprudence) to file the lawsuit on behalf of others. In the appeal, Ms. Kjolsrud "concedes she hadn't read the brochures before filing her action." However, the appeal also noted that after the lawsuit was filed the abortion clinic updated their brochure to the following:
� "Some anti-abortion activists claim that having an abortion increases the risk of developing breast cancer. A substantial body of medical research indicates that there's no established link between abortion and breast cancer. In fact, the National Cancer Institute has stated, '[t]here is no evidence of a direct relationship between breast cancer and either induced or spontaneous abortion.'"

Carroll

Patrick S. Carroll published a statistical analysis in the Journal of American Physicians and Surgeons, a politically conservative journal with a pro-life stance. The study claimed that, among seven risk factors, abortion was the "best predictor of breast cancer," and fertility was also a useful predictor. It forecasts, for the year 2025, higher breast cancer rates for Czech Republic, England and Sweden and lower for Finland and Denmark based on abortion trends. Carroll's study was criticized by a Guardian editor, who alleged that the study's methodology was flawed and noted that it was funded by an anti-abortion group and published in a "right wing" journal.

Criticism of media coverage

In an article titled "Blinded by Science" for the Columbia Journalism Review, Chris Mooney argues that "balanced" coverage by the media of the ABC hypothesis, among other scientific hypotheses championed by the religious right, is an example of how the scientific fringe manipulates public opinion by insisting on the illusory notion of journalistic "balance" instead of scientific accuracy. In the article, Mooney criticizes John Carroll (former Editor-in-Chief of the Los Angeles Times), for a rebuke Carroll made regarding an article written by Scott Gold about the ABC hypothesis for the L.A. Times. Gold's article covered the National Cancer Institute (NCI) workshop, and Carroll notes that when a scientific advocate (Joel Brind) for the ABC hypothesis is found:

It isn't until the last three paragraphs of the story that we finally surface a professor of biology and endocrinology who believes the abortion/cancer connection is valid. But do we quote him as to why he believes this? No. We quote his political views.
Apparently the scientific argument for the anti-abortion side is so absurd that we don't need to waste our readers' time with it.

Carroll's concern is that Gold's article provides fodder to critics who claim that the L.A. Times has a liberal bias. Mooney writes in defense of Gold that:

As a general rule, journalists should treat fringe scientific claims with considerable skepticism, and find out what major peer-reviewed papers or assessments have to say about them. Moreover, they should adhere to the principle that the more outlandish or dramatic the claim, the more skepticism it warrants. The Los Angeles Times’s Carroll observes that “every good journalist has a bit of a contrarian in his soul,” but it's precisely this impulse that can lead reporters astray. The fact is, nonscientist journalists can all too easily fall for scientific-sounding claims that they can’t adequately evaluate on their own.

Responding to criticism Carroll reiterated:

You have an obligation to find a scientist, and if the scientist has something to say, then you can subject the scientist’s views to rigorous examination.

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