Abortion-breast cancer hypothesis

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The abortion-breast cancer (ABC) hypothesis (supporters call it the abortion-breast cancer link) posits induced abortion increases the risk of developing breast cancer;[1] it is a controversial subject and the current scientific consensus has concluded there is no significant association between first-trimester abortion and breast cancer risk.[2][3][4]

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 maturity in the third trimester – then more relatively vulnerable immature cells could be left than there were prior to the pregnancy, resulting in a greater potential risk of breast cancer. The hypothesis mechanism was first proposed and explored in rat studies conducted in the 1980s.[5][6][7]

The American Cancer Society concludes that presently the evidence does not support a causal abortion-breast cancer association,[8] yet pro-life activists like Dr. Joel Brind, Dr. Angela Lanfranchi and Karen Malec continue to champion a causal link.[4] In the past, pro-life advocates have sought legal action regarding disclosure of the abortion-breast cancer issue. This brought short-term legal and political intervention culminating with the Bush Administration changing the National Cancer Institute (NCI) fact sheet from concluding no link to a more ambiguous assessment.[9] 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 is not associated with an increase in breast cancer risk."[10]

Though the scientific community is largely skeptical of the hypothesis and has been rejected by some;[9][10] the ongoing promotion of an abortion-breast cancer "link" by pro-life advocates and medical associations is seen by others as merely a part of the current pro-life "women-centered" strategy against abortion.[11][12][13] Pro-life groups maintain they are providing legally necessary informed consent;[14] a concern shared by conservative Congressman Dr. Dave Weldon.[15] While early research indicated a correlation between breast cancer and abortion;[16][17] the current scientific consensus has solidified with the publication of large prospective cohort studies which find no clear association between abortion and breast cancer.[18][19] These studies along with all relevant research strive to remove from their results the many confounding factors, such as delayed child bearing (parity), which affect breast cancer risk apart from abortion. The abortion-breast cancer hypothesis continues to incite mostly political and some scientific debate.[4]

Contents

[edit] Proposed mechanism

Lobules pointed to by number 3, ducts are number 6.
Lobules pointed to by number 3,
ducts are number 6.

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:

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.[20] Russo and Russo have shown that mature breast cells have more time for DNA repair with longer cell cycles[21] which would account for the reduced risk of parturition against the baseline risk for women who have never conceived and those who have conceived and terminated their pregnancies.[5]

Later on Russo et al. found that placental human chorionic gonadotropin (hCG) induces the synthesis of inhibin by the mammary epithelium.[22][23] Bernstein et al. independently observed a reduced breast cancer risk when women were injected with hCG for weight loss or infertility treatment.[24] 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."[19]

[edit] Proponents

Dr. Joel Brind is the primary advocate of an abortion-breast cancer hypothesis. After converting to Christianity in 1985, Brind began to devote himself to the pro-life movement. He has worked as a consultant and expert witness for pro-life groups like Christ's Bride Ministries, and has fought against the legalization of RU-486. In his testimony at a federal hearing, Brind submitted that "thousands upon thousands" of women would develop breast cancer as a result of using the drug.

In 1996, Brind published a meta-analysis which was immediately criticized in a Journal of the National Cancer Institute editorial by Drs. Weed and Kramer for concluding response bias was unlikely to have affected their results, "dismissal of the study's limitations, and their blurring of association with causation."[25] 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,[4] national organization which lobbies for legislation recognizing an abortion-breast cancer link.

[edit] Background

The first study involving statistics on abortion and breast cancer was a broad study in 1957,[4] which examined common cancers in Japan. The researchers were cautious about drawing any conclusions from their unreliable methodologies. During the 1960s several studies by Brian MacMahon et al. in Europe and Asia touched on a correlation between abortion and breast cancer. Their results were summarized by the Journal of the National Cancer Institute in 1973 which inaccurately[4] concluded that "where a relationship was observed, abortion was associated with increased, not decreased, risk."[26] 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.

[edit] 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.[5] However, they did find that pregnancy and lactation provided a protective measure against various forms of benign lesions, like hyperplastic alveolar nodules and cysts. While results did suggest that rats who had interrupted pregnancies might be subject to "similar or even higher incidence of benign lesions" than virgin rats, there was no evidence to suggest that abortion would result in a higher incidence of carcinogenesis. A more thorough examination of the phenomenon was conducted in 1982, which confirmed the results.[6] A later study in 1987 further explained their previous findings.[7] 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.[7][21]

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.[27] 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.[28]

[edit] 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 does not 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.[29] 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.[30] 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.

[edit] 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[31] 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 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.[32] Premature birth adds further complications since uncorroborated studies have indicated it is associated with a history of induced abortion[33] and higher breast cancer risk.[34] 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.[35]

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 U.S. federal carcinogen list in December 2002. The American Cancer Society (ACS)[36] and the National Cancer Institute (NCI)[37] note reproductive hormones can elevate breast cancer risk.[38] 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.[39]

The controversial nature of abortion may introduce response bias into interview studies, especially for studies done in decades past when abortion was less accepted;[25] however, the significance of bias has yet to be confirmed. In the late 20th century there was some concern of an increase of breast cancer incidence. This was found to be partly due to longer lifespans, and the development of better detection methods capable of finding breast cancer earlier.[40]

[edit] Cohorts

[edit] 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).[17] The results indicated a increased 1.9 (1.2 - 3.0) RR for induced abortion and 1.5 (0.7 - 3.7) 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 point out it examined only very young women and did not account for some confounding factors such as family history of breast cancer.[41] 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).[42]

[edit] Lindefors-Harris

Another cohort study by Dr. 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).[43] 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 did not 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."[43]

The study was funded by Family Health International,[43] a pro-choice NGO and although the study started with 49,000 "after 11 years she had fewer than 5,000" who stayed in the study.[44] Lindefors-Harris made no adjustments for family history of breast cancer and the pill,[43] and provides no explanation for a lack of a control group or why the study was limited to women with an abortion before 30 years of age. Brind contends correcting for either of these removes the 23% "protective" effect; and that the study did not account for the difference of nulliparous women in the cohort 41% in comparison to 49% in the general population.[45] Possibly making the protective result about parity (childbearing) rather than abortion.

[edit] 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).[18] 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 legal in Denmark. The relative risk after statistical adjustment came to 1.00 (0.94 - 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 have been supported by the majority of cancer and gynecological organizations, such as NCI, ACOG, ACS, RCOG and Planned Parenthood, who use it as evidence when they state that the best scientific evidence does not support an ABC link.[9][46]

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.[47] 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 was not 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.[47] 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."[47] Dr. Brind has stated that he is against the use of just statistical adjustment and that standard case-control matching may more accurately account for birth-cohort differences.[48]

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.[49] 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."[49][5] The first section of Table 1 in the Melbye study:

Week of gestation No. of Cancers Person-Years Relative Risk (95% CI) * Multivariate Relative Risk (95% CI) †
<7 36 82 000 0.81 (0.58-1.13) 0.81 (0.58-1.13)
7-8 526 1 012 000 1.01 (0.89-1.14) 1.01 (0.89-1.14)
9-10‡ 534 1 118 000 1 1
11-12 205 422 000 1.12 (0.95-1.31) 1.12 (0.95-1.31)
13-14 6 14 000 1.13 (0.50-2.52) 1.13 (0.51-2.53)
15-18 17 35 000 1.24 (0.76-2.01) 1.23 (0.76-2.00)
>18 14 14 000 1.92 (1.13-3.26) 1.89 (1.11-3.22)

* 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 a relative 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); both results were statistically insignificant.

[edit] Michels

A study by Dr. Michels et al. (2007) from the Harvard School of Public Health containing 105,716 women (233/1,225 breast cancer cases/controls) concluded with a relative risk of 1.01 (0.88 - 1.17) "after adjustment for established breast cancer risk factors."[19] Some of the results lead the study to stipulate: "Although our data are not compatible with any substantial overall relation between induced abortion and breast cancer, we cannot exclude a modest association in subgroups defined by known breast cancer risk factors, timing of abortion, or parity." This modest association was mostly not statistically significant. The following are induced abortion results from Table 4 of the Michels study, with parity distinguished between nulliparous (no children) and parous (had children):

Parity* No. of Breast Cancer Cases† No. of Person-Years Age-Adjusted HR (95% CI) Covariate-Adjusted HR (95% CI)‡ P Value for the Test of Heterogeneity
Nulliparous
 No induced abortion 243§ 159 290 1 [Reference] 1 [Reference]
  Abortion
   ER+ 42 34 862 1.27 (0.90-1.79) 1.25 (0.87-1.78) .65
   ER− 14 34 884 1.45 (0.79-2.68) 1.35 (0.71-2.58)
   PR+ 33 34 865 1.49 (1.00-2.22) 1.39 (0.92-2.11) .73
   PR− 12 34 889 1.25 (0.65-2.40) 0.97 (0.49-1.93)
Parous
 No induced abortion 962|| 642 741 1 [Reference] 1 [Reference]
  Abortion
   ER+ 99 112 347 0.99 (0.80-1.23) 0.95 (0.77-1.18) .40
   ER− 35 112 405 1.17 (0.81-1.69) 1.20 (0.83-1.74)
   PR+ 59 112 382 0.84 (0.64-1.11) 0.80 (0.60-1.05) .002
   PR− 47 112 393 1.62 (1.17-2.23) 1.58 (1.13-2.20)

Abbreviations: CI, confidence interval; ER+, estrogen receptor positive; ER−, estrogen receptor negative; HR, hazard ratio; PR+, progesterone receptor positive; PR−, progesterone receptor negative.

* Parity status was updated in the regression analysis at every 2-year interval. The number of women who were nulliparous and reported spontaneous abortions was too small to calculate reasonably stable estimates.

† Cases with ER information and cases with PR information may overlap.

‡ The HRs and 95% CIs among nulliparous women were adjusted for age, birth weight, premature birth, family history of breast cancer, history of benign breast disease, height, body mass index at the age of 18 years and current body mass index (calculated as weight in kilograms divided by height in meters squared), age at menarche, oral contraceptive use, alcohol consumption, physical activity, menopausal status, age at menopause, and postmenopausal hormone use. The HRs and 95% CIs among parous women were adjusted for the same covariates as the HRs and 95% CIs among nulliparous women and in addition for parity and age at first birth.

§ Total number of cases, including 149 ER+ and 42 ER− (a total of 191 cases with known ER status), and 99 PR+ and 41 PR− (a total of 140 cases with known PR status) cases. The incidence of breast cancer with corresponding ER/PR status was used when calculating HRs of ER+, ER−, PR+, and PR− breast cancer.

|| Total number of cases, including 586 ER+ and 174 ER− (a total of 760 cases with known ER status), and 413 PR+ and 172 PR− (a total of 585 cases with known PR status) cases. The incidence of breast cancer with corresponding ER/PR status was used when calculating HRs of ER+, ER−, PR+, and PR− breast cancer.

[edit] Further cohort studies

Several other 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 (746/2,908 breast cancer cases/controls), published in 2006, found no significant ABC risk.[50] 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.[51]

[edit] Meta-analysis

[edit] Beral

In March 2004, Dr. Beral et al. published a study in The Lancet as a collaborative reanalysis on Breast cancer and abortion.[52] 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). Organizations and media outlets referenced the Beral study as the most comprehensive overview of the ABC evidence.[53][54]

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.[55] 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.[56]

[edit] Brind

Dr. Brind et al. (1996) conducted a meta-analysis of 23 epidemiologic studies.[57] 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.[46]

The Royal College of Obstetricians and Gynaecologists (RCOG) 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." However, in 2003 the RCOG concluded that there was no link between abortion and breast cancer.[58] Some of the ABC studies RCOG reference as evidence (pg. 77) have been heavily criticized by Brind in 2005.[42]

[edit] 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.[59] Included are a few interview studies of note.

[edit] 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.[60] 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).[16] The study also found a significant relative risk of 2.0 (1.2 - 3.3) for nulliparous women with an induced abortion at less than 8 weeks gestation. Daling et al. concluded that:

“ There was no excess risk of breast cancer associated with induced abortion among parous women. These data support the hypothesis that there may be a small increase in the risk of breast cancer related to a history of induced abortion among young women of reproductive age. However, the data from this study and others do not permit a causal interpretation at this time; neither do the collective results of the studies suggest that there is a subgroup of women in whom the relative risk associated with induced abortion is unusually high.[16] ”

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. However, Rookus (1996) study noted that patients with cervical cancer may report differently than breast cancer patients.[61]

[edit] 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 did not put one at greater risk.[62] Since induced abortion is common, legal, and even mandated by the government in China, the recall bias was minimized.[46]

Brind has argued that the same factors that make the Chinese study ideal for reducing recall bias also makes them inappropriate for comparison to the West.[63] 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.[62] This differs from North America.[32]

[edit] Response bias

Book cover of Breast Cancer: Its Link to Abortion and the Birth Control Pill
Book cover of Breast Cancer: Its Link to Abortion and the Birth Control Pill

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.[61] When this occurs then it artificially creates an ABC link where none exists. Three major studies have been published examining abortion response bias.

An editorial by Drs. Weed and Kramer focused on how Brind's meta-analysis dismissed bias as a factor. The editorial cites a 1991 Lindefors-Harris study[64] that used a "registry-based gold standard to show that healthy women consistently and widely underreport their history of abortion."[25] Drs. Weed and Kramer considered this compelling evidence there could be systematic bias within the studies included in the meta-analysis. However, subsequently the Lindefors-Harris conclusion was quietly retracted in 1998.[56] Drs. Weed and Kramer believed a causal conclusion was a "leap beyond the bounds of inference" and concluded:

Because bias impedes our vision and is subject to sound inquiry, we are far from reaching a scientific "limit". 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.[25]

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 association between abortion and breast cancer.[65] 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 (i.e., one of the causes), the study might be considered invalid based upon 'recall bias.'[66]

[edit] Lindefors-Harris

The Lindefors-Harris (1991) study (317/512 breast cancer cases/controls) was the first major study to examine response and recall bias.[64] 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.[64]

The 1994 Daling study examined the findings on overreporting of the Lindefors-Harris study and found it "reasonable to assume that virtually no women who truly did not have an abortion would claim to have had one,"[60] and missing records could have occurred for a variety of reasons. With these eight women removed the error margin was reduced from 50% to 16% which severely limited its statistical significance. Dr. Brind believes the remaining 16% could have resulted from the Swedish fertility registry[67] – where women were interviewed as mothers – which could have increased their tendency to underreport, given that a mother might not want to appear unfit.[57] Subsequently Dr. Lindefors-Harris retracted the 50% conclusion in 1998, but they reasserted since the Melbye cohort study in 1997 found no significant ABC risk, the 30% increased risk in the Brind meta-analysis must be the accumulative result of response bias.[56]

[edit] Rookus

The Rookus (1996) study (918 breast cancer cases/controls) compared two regions in the Netherlands to assess the effect of religion on ABC results based on interviews.[61] 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, Brind et al. pointed out that it was attained with an extremely small sample size.[68] (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 has not been ruled out convincingly."[61]

[edit] Tang

A study by Dr. Tang et. al. (2000) (225/303 breast cancer cases/controls) done in Washington State found controls were not more reluctant to report induced abortion than women with breast cancer.[69] Their results were that 14.0% of cases and 14.9% controls (a difference of -0.9%) did not 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,[70] and a predominantly Roman Catholic population in the Rookus study.[61]

[edit] Spontaneous abortion

Studies of spontaneous abortions (miscarriages) have generally shown no increase in breast cancer risk,[71] although a study by Dr. Paoletti concluded there is a "suggestion of increased risk" 1.2 (0.92 - 1.56) after 3 or more pregnancy losses.[72] 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.[12]

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.[73] Kunz & Keller (1976) showed that when progesterone is abnormally low a miscarriage occurs 89% of the time.[74] Advocates of the ABC hypothesis argue that, given the association of most first trimester miscarriages with low hormone levels, spontaneous abortion is not analogous to an induced abortion.

[edit] 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.[4]

Pro-life organizations like National Right to Life turned to legal tactics that included lobbying against late-term abortions and RU-486. One of the other tactics adopted by the mainstream pro-life movement was promoting an alleged "ABC link". During the height of a publicized "breast cancer epidemic" pro-life organizations began to emphasize preliminary positive ABC results in an effort to further restrict abortion and to discourage women from having abortions.[4] Currently, pro-life organizations lobby to increase obstacles to abortion, such as mandated counseling, waiting periods, and parental notification,[32] and some feel that pro-life advocates treat ABC as simply another tactic in their campaign against abortion.[12] There have been ongoing and incremental legal challenges to abortion in the United States by pro-life groups.[75] 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.[76] The Canadian Breast Cancer Foundation was concerned the billboards misrepresented the state of scientific knowledge on the subject.[52]

The continued focus on the "ABC link" by pro-life groups has created a confrontational political environment. Pro-choice advocates and scientists alike have responded with criticisms.[4][18][25] The claims by pro-life advocates are sometimes referred to as pseudoscience.[77][78] The extent with which politics has infused the ABC issue is illustrated by an editorial that quoted Dr. Daling as saying:

“ 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.[79][80] ”

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.[81] 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.[82] In it Weldon expressed concern that the majority of studies indicate a possible ABC link and the politicization of the ABC issue is "preventing vital information from being given to women."[15]

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.[83] 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.[84] 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 hypothesis possibility prior to having an abortion.[85]

[edit] 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:

“ [T]he possible relationship between abortion and breast cancer has been examined in over thirty published studies since 1957. Some studies have reported statistically significant evidence of an increased risk of breast cancer in women who have had abortions, while others have merely suggested an increased risk. Other studies have found no increase in risk among women who have had an interrupted pregnancy.[9] ”

This alteration, which suggested that there was scientific uncertainty on the ABC issue, prompted an editorial in the New York Times describing it as an "egregious distortion" and a letter to the Secretary of Health and Human Services from members of Congress.[9] In response to the alteration, NCI convened a three-day consensus workshop. The workshop concluded that induced abortion does not increase a woman's risk of breast cancer, and that the evidence for this was well-established.[10] Afterwards, the director of epidemiology research for the American Cancer Society said, “This issue has been resolved scientifically . . . . This is essentially a political debate."[9]

Dr. Brind was the only one to file a dissenting opinion as a minority report criticizing the NCI's and Melbye's conclusions.[86][87] 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.[34]

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."[4] Dr. Lawrence R. Huntoon editor-in-chief for the conservative Journal of American Physicians and Surgeons notes in a Malec article that while the workshop had over 100 experts who voted on the findings the NCI website does not elaborate on the vote results.[88]

[edit] 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.[89] 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."[90] (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 1996 fact sheet that stated there was "no established link", instead of the 1999 fact sheet wording of "inconsistent" evidence for the ABC issue.[91][92] 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."[78]

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."[93] 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.[82]

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.[94] 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."[95] 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.'"

[edit] Carroll

Patrick S. Carroll published a statistical analysis in the Journal of American Physicians and Surgeons,[96] a politically conservative journal with a pro-life stance.[97] 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.[98]

[edit] 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.[99] 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 is not 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.[100]

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 is 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.[101]

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.[101]

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  99. ^ THE NATION; Texas OKs Disputed Abortion Legislation. Los Angeles Times. Retrieved on 2008-03-04.
  100. ^ John Carroll. L.A. Observed: John Carroll memo. laobserved.com. Retrieved on 2008-03-04.
  101. ^ a b Chris Mooney. CJR November/December 2004: Blinded by Science. Columbia Journalism Review. Retrieved on 2007-12-24.

[edit] External links

Pro-choice:

Pro-life: