Abortion-breast cancer hypothesis

The abortion-breast cancer (ABC) hypothesis (also referred to by supporters as the abortion-breast cancer link) posits a causal relationship between induced abortion and an increased risk of developing breast cancer. In early pregnancy, levels of estrogen increase, leading to breast growth in preparation for lactation. The hypothesis proposes that if this process is interrupted by an abortion – before full differentiation in the third trimester – then more relatively vulnerable undifferentiated cells could be left than there were prior to the pregnancy, resulting in a greater potential risk of breast cancer. The hypothesis garnered renewed interest from rat studies conducted in the 1980s;  however, it has not been scientifically verified in humans, and abortion is not considered a breast cancer risk by any major cancer organization.

A large epidemiological study by Mads Melbye et al. in 1997, with data from two national registries in Denmark, reported the correlation to be negligible to non-existent after statistical adjustment. The National Cancer Institute conducted an official workshop with over 100 experts on the issue in February 2003, which concluded with its highest strength rating for the selected evidence that "induced abortion is not associated with an increase in breast cancer risk." In 2004, Beral et al. published a collaborative reanalysis of 53 epidemiological studies and concluded that abortion does "not increase a woman's risk of developing breast cancer."

Critics of these studies argue they are subject to selection bias, that the majority of interview-based studies have indicated a link, and that some are statistically significant. Debate remains as to the reliability of these retrospective studies because of possible response bias. The current scientific consensus that abortion does not increase the risk of breast cancer has solidified with the publication of large prospective cohort studies which find no significant association between abortion and breast cancer. The ongoing prominence of the abortion-breast cancer hypothesis, despite the lack of clear scientific evidence, is seen by some as a part of the current pro-life "women-centered" strategy against abortion. Nevertheless, the subject continues to be one of mostly political but some scientific contention.

Politicization
Pro-life organizations lobby to increase obstacles to abortion, such as mandated counseling, waiting periods, and parental notification, and some feel that pro-life advocates treat ABC as simply another tactic in their campaign against abortion. There has been ongoing and incremental legal challenges to abortion in the United States by pro-life groups. 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.

The continued focus on the "ABC link" by pro-life groups has led to a backlash by pro-choice advocates, which has created a confrontational political environment at the expense of science. As a result, the ABC hypothesis is referred to as pseudoscience by a few pro-choice organizations. Studies are dismissed if their results contradict the current consensus of no ABC association, but others that refute the ABC hypothesis are supported uncritically. The extent with which politics has infused the ABC issue is illustrated by an interview with Dr. Daling that was published on September 28th, 1997 by the Los Angeles Daily News. In it she made the following statement:

If politics gets involved in science, it will really hold back the progress we make. I have three sisters with breast cancer, and I resent people messing with the scientific data to further their own agenda, be they pro-choice or pro-life. I would have loved to have found no association between breast cancer and abortion, but our research is rock solid, and our data is accurate. It's not a matter of believing. It's a matter of what is.

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. In it Weldon expressed concern over studies indicating an ABC link and the politicization of the ABC issue "preventing vital information from being given to women." Congressman Tom Bliley led an investigation into the representation of the ABC issue by the NCI, resulting in the NCI updating their website.

NCI workshop
The National Cancer Institute (NCI) conducted a workshop to evaluate the scientific evidence regarding the abortion-breast cancer hypothesis. This was done in response to alterations to the NCI website by the Bush administration in November 2002, which prompted an editorial in the New York Times and members of Congress writing a letter to the Secretary of Health and Human Services. The workshop concluded that the evidence was well-established that abortion did not increase a woman's risk of breast cancer.

Dr. Joel Brind, a pro-life activist, and the primary advocate of an abortion-breast cancer link and an invitee to the workshop, filed a dissenting opinion criticizing the NCI's and Melbye's conclusions. 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" (no evidence available) even though there was preliminary evidence of a correlation with higher breast cancer risk. Brind also asserts that many invited scientists had a conflict of interest because they were dependent on the NCI or other federal agencies for grants.

Scientific studies
Abortion-breast cancer studies have been conducted since 1957, but research relevant to the current ABC discussion, focuses on recent large cohort studies, a few meta-analyses, many case-control studies and then several experiments with rats.

The majority of the results in epidemiology are calculated as a relative risk. For example 1.0 (0.95 - 1.04) is no change in risk, whereas 1.51 is a 51% increased risk and 0.7 is a 30% decreased risk. It is followed by a 95% confidence interval in brackets that shows the actual risk has a 95% chance of being within the range given, so that (0.95 - 1.04) is the margin of error and there is a potential range of 5% decreased or a 4% increased risk. With more data the confidence interval becomes smaller; making it an indicator of the result's statistical reliability.

Confounding factors and hormones
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 women with no abortion history (control) – if this was not 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. Premature birth adds further complications since an uncorroborated studies have indicated it is associated with a history of induced abortion and higher breast cancer risk. One of the most significant controllable factors for breast cancer is parity, or the number of children a women has given birth to. With each full-term pregnancy (particularly the first) the breasts undergo growth and differentiation (in the third trimester); consequently, having no children can increase breast cancer risk.

All of these confounding factors have an effect, directly or indirectly, on hormones which impact breast cancer risk, but they do not 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 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. In the late 20th century there was some concern of an increase of breast cancer incidence. This was found to be partly due to women living longer, and that better detection methods were finding breast cancer earlier.

Melbye
A large, highly regarded ABC study was published by 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 – 8,908 controls). Of those women, 280,965 of them had induced abortions recorded in the computerized registry, which was started in 1973 when having an induced abortion through 12 weeks was fully legalized in Denmark. The relative risk after statistical adjustment came to 1.00 (0.94 to 1.06); meaning there was zero percent increase or decrease in breast cancer risk. This led to the conclusion that "induced abortions have no overall effect on the risk of breast cancer." The Melbye study's conclusions garnered great attention from the media and many organizations such as the NCI and Planned Parenthood, who use it as a foundation to argue that the best scientific evidence does not support an ABC link.

The Melbye study used women born from 1935 to 1978, but the computerized registry of induced abortions only started in 1973. As a result, Dr. Brind found that more than 30,000 women had been misclassified as having no abortion because the induced abortion occurred prior to 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. Their statistically adjusted relative risks indicated this was not the case. Drs. Brind and Chinchilli had concerns about the Melbye study database and how they statistically adjusted their overall relative risk. They argue that Dr. Melbye et al. adjusted out induced abortion from the overall results as they collectively removed confounding factors that increased over time (eg. smoking, late child bearing, obesity, etc.) and finding no ABC risk was a consequence and a red flag. Dr. Melbye et al. found the point to be self-contradictory, considering Dr. Brind wanted birth-cohort matching, then argued against "taking birth-cohort differences into account." Dr. Brind clarifies he is against the use of just statistical adjustment and that standard case-control matching may more accurately account for birth-cohort differences.

Another letter to the editor from Drs. Senghas and Dolan questioned why a statistically significant result for induced abortions done after 18 weeks gestation was not specifically addressed in the results section of the Melbye study abstract. Melbye et al. explained that even though the result was "in line with the hypothesis of Russo and Russo," they deemed the number of cancer cases small and did not want to overstate the finding. The first section of Table 1 in the Melbye study:

* The relative risks were calculated separately for each of the five variables, with adjustment for women's age, calendar period, parity, and age at delivery of a first child. CI denotes confidence interval. †Values were adjusted for women's age, calendar period, parity, age at delivery of a first child, and the other variables shown in the table. ‡The women with this characteristic served as the reference group.

Other sections listed age at induced abortion, number of induced abortions, time since induced abortion, and time of induced abortion and live-birth history. There was an indication of an elevated risk of 1.29 (0.80-2.08) for 12-19 year olds (relative to 20-24 subcohort), and a protective effect 0.74 (0.41-1.33) for women with an induced abortion before and after their first live birth (relative to induced abortion after 1st live birth subcohort).

Howe
The 1989 study by 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 – 1,451 controls). The results indicated a significant 1.9 (1.2-3.0) increased risk for induced abortion and an insignificant 1.5 (0.7-3.7) increase for spontaneous abortion. The authors believed that the study was inconclusive, but raised new questions for continuing research as women's recorded contraceptive histories grew.

Dr. Newcomb and Michels pointed out it examined only very young women and did not account for some confounding factors such as family history of breast cancer. However, the study is significant evidence that the positive ABC results in interview studies were not purely a result of response bias. Scott Somerville of the conservative group Accuracy in Media claims that it took a long time for Howe's study to be published due to a number of American journals that rejected the article. The Howe study was published in the Britain-based International Journal of Epidemiology in 1989.

Further cohort studies
Another cohort study by Lindefors-Harris et al. (1989) was done looking at 49,000 women who had received abortions before the age of 30 in Sweden (65 breast cancer cases – compared with estimate of occurrence in general population). Although reported by some sources as being a "large" cohort study the actual number of breast cancer cases is a fraction of most other studies. The risk for women who'd given birth previous to the abortion was 0.58 (0.38-0.84), whereas women with no births had an insignificant risk increase of 1.09 (0.71-1.56). Overall, the relative risk was 0.77 (0.58-0.99), making for a 23% reduced risk in comparison to "contemporary Swedish population with due consideration to age." The conservative political group Accuracy in Media (AIM) criticized the Lindefors-Harris study, claiming that the Lindefors-Harris control group was not well-defined and did not account for differences between how Swedish and American women use abortion. AIM also alleged bias in the study because funding came from Family Health International, a large pro-choice non-profit organization trying to meet the public health needs of the world's poorest people.

Several more recent prospective cohort studies have also found little evidence of a link between induced abortion and breast cancer. A study of 267,361 European women (1,657 breast cancer cases), published in 2006, found no significant ABC risk. Another 2006 study involving 267,400 women (unknown number of breast cancer cases) 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. Finally, a study from the Harvard School of Public Health, published in 2007 and containing 105,716 women (1,458 breast cancer cases), yet again found no ABC correlation "after adjustment for established breast cancer risk factors."

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 did not find evidence of a relationship between induced abortion and breast cancer, with a relative risk of 0.93 (0.89-0.96). Dr. Brind maintains this study is a meta-analysis rather than a "collaborative reanalysis" and like other meta-analyses is subject to selection bias. He also criticizes that Lindefors-Harris conceded in 1998 their initial response bias conclusion may have been unsound, but this was not noted by the Beral study which used Lindefors-Harris to support a response bias hypothesis to account for higher ABC risk found in interview based studies. Many organizations and media outlets have referenced the Beral collaborative reanalysis as the latest and most comprehensive overview of the ABC evidence.

Brind

A meta-analysis was conducted by Dr. Brind et al. (1996) with both pro-choice and pro-life scientists that examined 28 published studies. It concluded that there was on average a 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, not working with the raw data from several studies, and including some studies that have alleged methodological weaknesses. The Royal College of Obstetricians and Gynaecologists in March 2000 published evidence-based guidelines on women requesting induced abortion. The review of the available evidence at the time was "inconclusive" regarding the ABC link. They also noted "Brind's paper had no methodological shortcomings and could not be disregarded."

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. Here are a few interview studies of note.

Daling

Dr. Daling from the Fred Hutchinson Cancer Research Center headed two studies on the ABC issue looking at women in Washington state. The 1994 study results indicated a 1.5 (1.2-1.9) increased risk. 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 this study supported the ABC link, the overall results from epidemiologic studies are inconsistent.

The Daling study in 1996 resulted in a relative risk of 1.2 (1.0-1.5). The risk was highest among women without children who had abortions prior to 9 weeks gestation. Dr. Daling et al. examined the possibility of response bias by comparing results from two recent studies on invasive cervical cancer and ovarian cancer. The results argued against significant response bias. The Rookus (1996) study noted that patients with cervical cancer may report differently than breast cancer patients.

Sanderson

A 2001 study conducted in Shanghai, China by Dr. Sanderson from the University of South Carolina and South Carolina Cancer Center at Columbia concluded that there was no ABC link and that multiple abortions did not put one at greater risk. Since induced abortion is common, legal, and even mandated by the government in China, the recall bias was minimized.

Critics of the Chinese studies have said that the same factors that make them ideal for reducing recall bias also makes them inappropriate for comparison to the West. With the wide availability of abortion services, over 80% of them were done within the first eight weeks of gestation. In comparison only 55% of American women had an abortion before the ninth week. Due to China’s strict population control, the vast majority of the abortions in the Chinese study were done after the first full-term pregnancy, which had been relatively early. This is not reflected in North America.

Response bias
Response bias for ABC normally 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 in some places controversial, nature of abortion, which may cause some women to not want provide full disclosure. Women in the control group are more likely to have no serious illnesses, and hence have less motivation to be truthful than those trying to diagnose their problem. If this occurred then it would artificially create an ABC link where none existed. Two major studies have been published examining abortion response bias.

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 is no ABC link. However, some political foes of abortion point out there is no "plausible evidence of report bias" for those interview based studies. An editorial in the Journal of the National Cancer Institute examined the notion of epidemiology reaching its limit given the possibility of response bias putting results in doubt. It concluded:

Indeed, after this excursion into the issue of abortion, bias, and breast cancer, it seems our future has as much to do with human behavior as with human biology.

Lindefors-Harris

The Lindefors-Harris (1991) study 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 was not reflected in the records. It was decided that for the purposes of the study, these women did not have abortions.

Dr. Daling (1994) found it "reasonable to assume that virtually no women who truly did not have an abortion would claim to have had one," and missing records could have occurred for a variety of reasons. With these eight women removed the error margin is reduced from 50% to 16% which severely limits its statistical significance. Dr. Brind believes the remaining 16% could have resulted from the Swedish fertility registry – where women were interviewed as mothers – which could have increased their tendency to underreport, given that a mother might not want to appear unfit. Subsequently the Lindefors-Harris obliquely retracted the 50% conclusion in 1998, but reasserted since the Denmark (Melbye 1997) cohort study found no ABC correlation the 30% increased risk in the Brind meta-analysis must be the accumulative result of response bias.

Rookus

The Rookus (1996) study compared two regions in the Netherlands to assess the effect of religion on ABC results based on interviews. The secular (western) and conservative (southeastern) regions showed ABC relative risks of 1.3 (0.7-2.6) and 14.6 (1.8-120.0) respectively. Although this was a large variance, Dr. Brind et al. pointed out that it was attained with an extremely small sample size. (12 cases and 1 control)

Rookus et al. supported this 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 Brind's et al. letter clarifies it only indicated response bias between the two regions, not between case and control subjects within regions. Dr. Rookus et al. responded to the criticism by noting that there was 4.5 month underreporting difference between control and case subjects in the conservative region. This is indirect evidence for reporting bias since comfort with reporting oral contraception should be 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%) did not report registered induced abortions. They concluded that finding a causal ABC link would be a disservice to the public, and epidemiologic research if "bias has not been ruled out convincingly."

Rats
Drs. Russo & Russo from the Fox Chase Cancer Center in Philadelphia conducted a study in 1980 which found that rats who received abortions had a "similar or even higher incidence of benign lesions" and carcinomas than virgin rats of matching age. A more thorough examination of the phenomenon was conducted in 1982, which confirmed the results. A later study in 1987 further explained their previous findings. After differentiation of the mammary gland resulting from a full-term pregnancy of the rat, the rate of cell division decreases and the cell cycle length increases, allowing more time for DNA repair.

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 and Drs. Russo & Russo on the importance of the rat studies findings. Dr. Mor emphasizes that rat studies are ideal for understanding basic processes but it would be scientifically "wobbly" to extrapolate those findings to humans.

Spontaneous abortion
Studies of spontaneous abortions (miscarriages) have generally shown no increase in breast cancer risk, although a study by Dr. Paoletti concluded there is a "suggestion of increased risk" 1.2 (0.92 to 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 is proof that neither early pregnancy loss nor abortion are risk factors for breast cancer.

One of the problems with comparing miscarriage to abortion is the issue of hormone levels in early pregnancy, a key point because the ABC hypothesis rests on hormonal influence over breast tissue development. While it is true most miscarriages are not caused by low hormones, most miscarriages are characterized by low hormone levels. Kunz & Keller (1976) showed that when progesterone is abnormally low a miscarriage occurs 89% percent of the time. Advocates of an ABC link argue that, given the association of most miscarriages with abnormally low hormone levels, spontaneous abortion is not analogous to an induced abortion.

A distinction should also be made for second trimester miscarriages as their hormonal characteristics differ from first trimester miscarriages.

North Dakota lawsuit
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:


 * "It does appear that the clinic had the intent to put out correct information and that their information is not untrue or misleading in any way. They did exercise reasonable care... One thing is clear from the experts, and that is that there are inconsistencies. The issue seems to be in a state of flux."

The judge noted it was their "intent" to provide accurate information because the brochure used an outdated fact sheet. 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 are 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 is 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 should not 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 had not 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 is 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.'"

State laws
As of November 2004, women seeking abortions in Mississippi must first sign a form indicating they have been told abortion could increase their risk of breast cancer. In Texas, Louisiana, and Kansas, state law requires women receive a pamphlet that suggests a cancer link with abortion. Similar legislation requiring notification has also been introduced, and is pending, in 14 other states. An editor for the American Journal of Public Health expressed concern over how such legislative bills propose warnings that do not agree with established scientific findings. However, it is 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 link possibility prior to having an abortion.

Patrick Carroll
Patrick S. Carroll published a statistical analysis in the conservative and controversial Journal of American Physicians and Surgeons. 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. The study was funded by two pro-life groups and Carroll's organization "Pension and Population Research Institute" (PAPRI) appears small, low-profile and to be outside the scientific community.