User:RoyBoy/sandbox/ABC history

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History

Study methodology

Results in epidemiology are calculated as a relative risk with a confidence interval. The significance of a result can be contentious because of incomplete data, missed breast cancer confounding factors,[1][2][3] imprecise controls, or flawed statistical analysis.[4] Studies traditionally control for such factors using case-control methodology, matching each woman in a study who has had an abortion (case) with similar women with no abortion history (control).

The controversial nature of abortion introduces response bias into interview studies, especially for studies done in the past when abortion was less socially accepted.[5] The statistical significance of this bias has not been determined.[6][7][8] Research relevant to the current ABC consensus focuses on cohort studies using large population datasets; and meta-analyses which review and combine the numerous smaller interview case-control studies done.

Spontaneous abortion

Studies of spontaneous abortions (miscarriages) generally show little to no increase in breast cancer risk.[9][10] This has been used as evidence against the ABC hypothesis and pro-choice advocates have claimed it is proof that neither early pregnancy loss nor abortion are risk factors for breast cancer.[11][4] One of the problems with comparing miscarriage to abortion is hormone levels in early pregnancy, as 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.[12] Kunz & Keller (1976) established that low levels of progesterone was followed by miscarriage 89% of the time, and 92% for oestradiol;[13] making them better indicators of a threatened pregnancy than the 79% of human chorionic gonadotropin (hCG).

Early studies

The first study involving statistics on abortion and breast cancer (ABC) was a broad study in 1957 examining common cancers in Japan which found an ABC association.[4] The researchers were cautious about drawing any conclusions from their unreliable methodologies. During the late 1960s several studies by Brian MacMahon et al. in Europe and Asia touched on ABC correlations and their 1973 paper inaccurately[4] concluded that "abortion was associated with increased, not decreased, risk."[14] Russo & Russo from the Fox Chase Cancer Center in 1980 and 1982 examined the proposed ABC correlation. They found that rats who had interrupted pregnancies had no noticeable cancer risk increase[15][16] and had "similar or even higher incidence of benign lesions", but there was no evidence that abortion resulted in higher carcinogenesis.[4] A later study in 1987 clarified that when full-term pregnancy differentiates the mammary gland, cell division decreases and the cell cycle length increases, allowing more time for DNA repair.[17][18] Even though the studies found similar risk rates between virgin and abortion rats, their research was used to support higher ABC risk for the next twenty years.[19] However, because rats have neither breasts nor breast cancer, extrapolating to humans is viewed as dubious.[20]

ABC research began in earnest in the 1980s and by 1990 there were ~15 studies on the topic. The Pike et al. (1981) study focused on oral contraceptive use of young women and found an increased ABC risk for women with induced or spontaneous abortion before their first full term pregnancy.[4][21] This study caught the interest of Brind who then became involved in the topic. Dr. Vessey et al. (1982) study found Pike's results "provocative and worrying" so researchers at London and Oxford hospitals tried to verify it, they found no increased risk and their result was even "more compatible with protective effects".[22] Brind notes as only a "handful" of women in the dataset had a recorded abortion before their first full term pregnancy,[23] this resulted in the authors combining spontaneous and induced abortion sub-groups together.[24]

~in progress marker~

The first notable ABC record based study in 1989 was by Howe et al. examining young women with breast cancer in upstate New York.[25] While the results indicated an increased risk of 1.9 (1.2–3.0) the authors concluded that the small dataset was inconclusive as fertility patterns were changing dramatically as a result of legal abortion and increased use of contraceptives, and did not account for significant confounding factors such as family history.[26] In the early 1990s, there was growing concern of an increase in breast cancer incidence particularly among younger women. This was found to be mostly due to longer lifespans and the development of new detection methods capable of finding breast cancer earlier.[27] After suffering setbacks, notably President Clinton's Freedom of Access to Clinic Entrances Act in 1994 and political backlash from violence, the anti-abortion groups were in search of new tactics against abortion, so they began incorporating ABC findings into their new women-centered strategy.[4]

~in progress marker~

When Daling et al. (1994) from the Fred Hutchinson Cancer Research Center released their 1.5 (1.2-1.9) result Brind and anti-abortion activists seized on it and the small higher risk sub-group with poor controls as proof of their ABC link, while Daling was cautious and advised not taking "a firm conclusion at the time."[4][28] A larger follow up study by Daling et al. (1996) found a smaller 1.2 (1.0-1.5) risk and emphasized they found no sub-group with an unusually high risk and concluded that: "data from this study and others do not permit a causal interpretation at this time."[6] Daling et al. also examined the effect of response bias but did not find significant bias.[6] An accompanying editorial by Lynn Rosenberg of the Boston University School of Medicine outlined wider debates within epidemiology, pointing to recall bias as a explanation for abortion-breast cancer risk findings of questionable statistical importance. There was also questions as to why spontaneous abortion showed no increased risk. With this in mind the American Medical Association in 1995 warned that legislation based on abortion-breast cancer research were premature. With these editorials Brind viewed it as pro-abortion efforts to minimize an ABC link, so he increased his efforts in the anti-abortion press while fighting against the FDA approval of RU-486.[4]

Recall or response bias occurs when women intentionally "underreport" or deny their abortion history. Women in control groups are less likely to have serious illnesses, and for personal reasons have less motivation to be truthful than those trying to diagnose their problem.[7] If this occurs it artificially creates an ABC risk where none exists. The Lindefors-Harris (1991) study was the first major study to examine response bias.[29] Using data of two Swedish induced abortion studies it concluded there was a 1.5 (1.1 – 2.1) margin of error from recall bias. However, eight women in this error margin "overreported" their abortions, meaning they reported having an abortion that was not recorded, so the researchers concluded it did not happen.[29] The 1994 Daling study found it "reasonable to assume that virtually no women who truly did not have an abortion would claim to have had one."[28][30] With the overreporting removed the error margin went from 50% to 16%. Brind believes the remainder may be from the Swedish fertility registry[31] – where women were interviewed as new mothers – which could have increased underreporting.[32]

Notes: LH 1.5 conclusion widely reported, the criticism and retraction, not?

In 1996, Brind et al. published a meta-analysis of 23 epidemiologic studies finding on average a relative risk of 1.3 (1.2–1.4) increased risk of breast cancer.[32] The meta-analysis was criticized for selection bias by using studies with widely varying results, using different types of studies, not working with the raw data from several studies, and studies with possible methodological weaknesses.[5] The strong reaction[citation needed] to the study particularly in Britain and the United States prompted the Journal of Epidemiology & Community Health editor-in-chief Stuart Donnan, to write an editorial noting, "I believe that if you take a view (as I do), which is often called 'pro-choice', you need at the same time to have a view which might be called 'pro-information' without excessive paternalistic censorship (or interpretation) of the data."[33] An editorial by Weed and Kramer focused on how Brind's meta-analysis dismissed bias as a factor. The editorial cites the Lindefors-Harris (1991) response bias study that used a "registry-based gold standard to show that healthy women consistently and widely underreport their history of abortion."[5][29] Weed and Kramer considered this compelling evidence there could be systematic bias within the studies included in the meta-analysis and therefore a causal conclusion was a "leap beyond the bounds of inference" and concluded:


The Rookus et al. (1996) study compared two regions in the Netherlands to assess the effect of religion on ABC interview results.[7] The secular (western) and conservative (southeastern) regions indicated 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 came from a very small sample size with 1 control,[34] and does not reflect how good case-control studies are designed to compare women within, not between, regions. Rookus et al. 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. They concluded that Brind asserting a causal ABC link would be a disservice to the public and epidemiology when "bias has not been ruled out convincingly."[7]

Consensus studies

A large, highly regarded ABC study was published by Melbye et al. (1997) of the Statens Serum Institute in Copenhagen (1,338 ABC cases, no controls used) determined the overall relative risk after statistical adjustment came to 1.00 (0.94–1.06) or no increased breast cancer risk.[35][36] The study concluded that "induced abortions have no overall effect on the risk of breast cancer."[35] The Melbye study's conclusions have been used by many organizations, such as NCI, ACOG, ACS, RCOG and Planned Parenthood, determining that reliable scientific evidence shows no ABC link.[37][38] The statistical adjustments for the cohort effect, rather than standard case-control matching, is a concern of Brind who argues that the Melbye study accidentally adjusted out induced abortion from the overall results. As induced abortion has increased along many confounding factors (eg. smoking, late child bearing) within birth-cohorts, Brind believes the zero result after adjustments is a red flag overall ABC risk was removed along with other factors.[39][40] After Melbye the NCI updated their website to say: "there is no convincing evidence of a direct relationship between breast cancer and either induced or spontaneous abortion."[4] This in combination with Brind's phone ringing off the hook with anti-abortion supporters facing hard ABC questions, Brind engaged "any representative who would listen" and through pressure of Congressman Tom Coburn in July 1998 the NCI backtracked to ABC evidence being "inconsistent" on its fact sheet.[41][4]

A study by Tang et al. (2000) (225/303 ABC cases/controls) done in Washington State found controls were not more reluctant to report induced abortion than women with breast cancer.[8] Their results were that 14.0% of cases and 14.9% controls (an effect 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,[42] and a predominantly conservative population in the Rookus study.[7]

In March 2004, Beral et al. published a study in The Lancet as a collaborative reanalysis on Breast cancer and abortion.[43] This meta-analysis of 53 epidemiologic studies 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 have cited the Beral study as the most comprehensive overview of the ABC evidence.[44][45] Brind maintains this study is subject to selection bias, which he believes is reflected in the removal of 15 studies with positive ABC results for "unscientific reasons"; and including 28 unpublished studies that outnumber the remaining 24 peer reviewed studies.[46] Beral refers to the Lindefors-Harris recall bias study as an explanation for the removal of studies from their meta-analysis and ABC risk found in interview based studies,[29] however Brind notes in 1998 that Lindefors-Harris conceded their conclusion may have been unsound.[30]

A number of studies indicate an ABC risk[4] and several others a protective effect,[47][22] individually their small size and possible flaws has not shifted the scientific consensus which determines the best evidence disproves an abortion-breast cancer link.[48][49][50] The ABC discussion highlights how scientists can lose "control over how their results were interpreted or put to use. As a by-product of this process, they were also provoked into a closer examination of how various kinds of bias operate within their own discipline, and why apparently similar studies may produce dramatically different results," and "how tentative conclusions may become fossilized or reified as citations accumulate."[4] This led to scientific methods being influenced by the ABC narrative, ABC studies being contextualized by breast cancer risk increases, and ultimately incorporated into the intense abortion debate in the United States. Consequently those exploring the abortion issue face significant challenges to clarify its effect, if any, on women's health.[4]

Memes & stuff

Memes removed:

  • Melbye (others), risk among sub-groups, no RS secondary sources?
  • Melbye, reply gets Brind's position wrong, adds nothing.
  • Daling, pro-choice bias interpreting ABC results. Only independant source to do so, hence not a WP:Weight problem.
  • Sanderson, Chinese abortion not the same as Western use.
  • Rookus, guessing why Daling didn't find bias.
  • RCOG re Brind, outdated and shooting match stuff.
  • Melbye high-risk group, not good enough to make the abstract; not notable enough for article?
  • Remove Bartholomew, suggest" adds little, interview studies are not automatically bad; record based studies aren't automatically good (ie. Howe, which isn't subject to bias, just inadequate data).

Memes missing:

  • Melbye's dataset hasn't been reanalyzed with controls? Why not?
  • NCI workshop, Melbye positive risk sub-groups clarified & removed? Brind says unpublished data used, without proper review.
  • Pro-life legal tactics to delay / obstruct obtaining an abortion (part of women centric strategy)
  • Recall bias, Brind inaccurately accused of saying bias is "manufactured", actually was speaking to Rookus comparing dissimilar regions to get desired result; rather than within regions.
  • Recall bias, scientists call for it to be "ruled out", then don't seem to do the work until Tang (2000).
  • Recall bias, Tang (2000) any impact? Why not?
  • Recall bias, needs to be demonstrated per geographic (cultural) birth-cohort. Not extrapolated from one population to another.
  • Media & medical bodies, accepting null/negative results, criticizing (not reporting) positive results.

Memes in need of better sourcing/prose:

  • Minority of studies showing protective effect, include near end with study overview as not impacting consensus.
  • Pro-life relying on interview study evidence and tentative conclusion(s).

Original research:

  • RoyBoy (seeking secondary source): Using a potential ABC risk (without conceding there is one) as a pro-choice legal tactic in the U.S., as a counter to the onerous legislation on abortion providers and women. Premised on delaying/reducing access to abortion violates women rights to "life and liberty" by restricting choices and increasing potential health risks for abortions done later in the pregnancy.

Primary cruft (reference)

Daling et al. (1996) examined the possibility of response bias by comparing results from two 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.[7]

The Royal College of Obstetricians and Gynaecologists (RCOG) in March 2000 published evidence-based guidelines where they noted "Brind's paper had no methodological shortcomings and could not be disregarded."[53] However, in 2003 the RCOG concluded that there was no link between abortion and breast cancer.[54]

However, subsequently the Lindefors-Harris conclusion was quietly retracted in 1998.[30]

Interview (case-control) based studies have been inconsistent on the ABC hypothesis. With the small numbers involved in each individual study and the possibility that response bias has skewed the results, the scientific consensus has focused on meta-analysis and record based studies which are typically much larger.[55]

2001 study Shanghai, China by Sanderson et al. no ABC link and that multiple abortions[56] vast majority of the abortions in the Chinese study were done after the first full-term pregnancy.[56] This differs from North America.[2]

Interview studies ongoing in 2000s (since Beral), but not impacting scientific consensus: Istanbul University, 2009[57]

A study by Michels et al. (2007) from the Harvard School of Public Health containing 105,716 women (233/1,225 ABC cases/controls) concluded with a relative risk of 1.01 (0.88 – 1.17) "after adjustment for established breast cancer risk factors."[58] Some of the results lead the authors 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."

Several other recent prospective cohort studies have also found little evidence of a link between induced abortion and breast cancer. A study published in 2006, found no significant ABC risk.[59]

Protective effect: Several studies have indicated a protective ABC effect,[47][10][60] however incomplete data,[61] lack of control group, failing to account for confounding factors,[62] have limited their impact on the ABC topic and consensus.

Several studies have indicated an induced abortion prevents breast cancer. Examples include: [43] selection bias, Scottish Brewster [10] unknown issues, [47] parity, no controls [62], Serbian Tumori,[63] small and only with (very?) parious women Harris et al. (1989) (65 ABC cases – 0 controls). overall risk of 0.8 (0.58 – 0.99), making for a 20% reduced risk in comparison to "contemporary Swedish population with due consideration to age."[47]Family Health International,[47] a pro-choice NGO 49,000 > 5,000 after 11 years. family history, the pill,[47] no control group. Brind nulliparous in the cohort 41% vs 49% in the general. protective childbearing

Other researchers asked why an increased risk sub-group for induced abortions after 18 weeks gestation was not in the Melbye study abstract.[64] 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."[15][64]

A review of ABC studies was conducted by 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 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]

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