Overview: Breast Cancer and the Pill

Document Title: lifeissues | Overview: Breast Cancer and the Pill


OVERVIEW: BREAST CANCER AND THE PILL



Chris Kahlenborn, M.D. Reproduced with permission

SUMMARY OF THE FDA (FOOD & DRUG ADMINISTRATION) PROCEEDINGS SUBJECT:
OVER-THE-COUNTER PRODUCTS DATE: JUNE 28-29, 2000



In May, 2000, I received word that the FDA planned to conduct hearings
for over-the-counter products (including the birth control pill), which
were held on June 28-29, 2000 in Gaithersburg, Maryland. I wrote to Miss
Desantis, the coordinator of this event. She stated that I would have
ten minutes (on Wednesday, June 28th) to present my findings about the
Pill and breast cancer.


The proceedings started at 8:30 AM and were coordinated by Dr. Robert
DeLap who is an internist with a special interest in medical oncology.
The meeting consisted of about 15 FDA administrators and about 750 to
1,000 people in the audience. Each speaker could speak for ten minutes
and then any member of the FDA could ask questions. The audience could
ask no questions. In addition, a handout was submitted to each of the
members of the FDA. Finally, we were told that we had until August 25th
to submit any written comments, which to my understanding, become part
of the public record as do all that was presented at the June 28-29
meetings.

I gave a short presentation most of which was included in my handout.
The major studies show that the birth control pill causes breast cancer
and that the Pill also causes invasive cervical cancer and early
abortions. I stated that 17 out of 20 retrospective studies since 1980
have shown that oral contraceptives increase the risk of breast cancer
by about 40% if taken prior to a woman’s first live-birth.

After my talk, a number of people came up to me including a lawyer and a
consulting group all of whom wanted to have more information about the
research and/or book. It appeared to me that the business and lay
community in the audience were receptive and that some of the members of
the FDA were cool, although Dr. DeLap did conduct the hearing fairly.

In addition, I noted that there were actually no talks in favor of
making the Pill over-the-counter, prior to my presentation, which is
something I did not expect. (Most of the talks were about making
Sunscreen Products more accessible or trying to get other medicines
over-the-counter). The next day the report on CNN national news made it
sound as if the entire FDA was pushing to have the Pill made
over-the-counter. I found this to be more than a simple distortion
(fabrication is the term I am looking for), since the only person who
spoke directly on the subject of the Pill was I! I told the FDA that I
would be submitting my entire book (Breast Cancer: Its Link to Abortion
and the Birth Control Pill) as part of the public record soon (the
deadline is August 25th, 2000). One reporter told me afterwards that he
was going to look at the FDA record for my book and would get the
information from my book.


Submitted:

Chris Kahlenborn, M.D. Presented Material: (The material on following
pages were both sent and presented to the FDA)



OVERVIEW: BREAST CANCER AND THE PILL



Chris Kahlenborn, M.D. Reproduced with permission



What is an oral contraceptive?



An oral contraceptive is usually a combination of a synthetic estrogen
and progestin (i.e., the two major types of female hormones) which women
take for 21 days out of a 28 day cycle. These hormones work by
suppressing, but not eliminating ovulation, thickening cervical mucus,
and by changing the lining of the uterus.

Is there any evidence that the OCP (oral contraceptive pill) causes
breast cancer in animals?



Yes. Concerns were raised in 1972 when it was noted that an oral
contraceptive pill containing the artificial hormones mestranol and
norethynodrel appeared to cause a case of metastatic breast cancer in a
group of six female rhesus monkeys [252]. This was especially worrisome
since rhesus monkeys rarely develop breast cancer. Until that time, only
three cases of breast cancer in rhesus monkeys were reported. Although
some argued that this was simply a "chance finding," concern grew
further when it was noted that both beagles and rodents developed breast
cancer when exposed to the hormones contained in today's OCPs [sources:
267, 268, 255, 313, 254].

How might OCPs cause breast cancer in humans?



In 1989, Anderson et al [174] published a classic paper regarding the
influence of the OCPs on the rate of breast cell division. They found
that nulliparous women (ie, women who have not had children) who took
OCPs had a significantly higher rate of breast cell division than
nulliparous women who did not take them. This was especially important
since it is known that in general, cells that divide more rapidly are
more vulnerable to carcinogens (ie, cancer producing agents) and thus
more likely to become cancerous.

Do oral contraceptives cause an early abortion and if so, could this
also be playing a role in the increased risk of breast cancer?



Both pro-life and pro-abortion groups openly admit that OCPs cause early
abortions, with the latter doing so publicly in testimony before the
Supreme Court in 1989 {The New York Times} [157]. Induced abortion
before a woman's first-term pregnancy has been noted to increase a
woman's risk of breast cancer by 50% [98]. Could an abortion (defined to
be the death of the zygote, embryo or fetus after conception has
occurred) within the first week after conception have a deleterious
effect as concerns breast cancer?. The hormonal physiology of early
pregnancy is difficult to measure but Stewart et al [240] and Norman et
al [368] have shown that estradiol and progesterone levels (ie, the
female hormones) start to rise above baseline levels within four days of
conception, thus prior to implantation and before hCG levels begin to
rise. An early abortion would cause a sudden fall in the levels of these
hormones. Could this early "hormonal blow" be playing a role? To this
author's knowledge, no one has asked or studied this question.

Can you give a brief history of the studies that showed a link between
the risk of taking OCPs prior to first term pregnancy and the increased
risk of breast cancer?



In 1981, Pike et al [138] found that women who took OCPs for four years
before their first term pregnancy had at least a 2.25 fold (125%)
increased risk of developing breast cancer before age 32. This startled
the research world and led to additional studies, including a very large
American trial called the CASH study (ie, Cancer And Steroid Hormone
study). In 1993, the CASH study showed that women who took OCPs prior to
first term pregnancy and were under 44 years of age had a 40% increased
risk in breast cancer, which reached statistically significance in the
35-44 age group [6].

Later in England, Chilvers et al [8] published the results of another
large study called the United Kingdom National Study. She showed that
young women under the age of 36 who had used oral contraceptives for at
least 4 years before their first term pregnancy had at least a 44%
increased risk in breast cancer. The last large study was performed in
1995 by Brinton et al [1]. It showed a 42% increased risk for women who
used OCPs for more than 6 months prior to having a full term pregnancy.

If the major studies showed the risks that you have just mentioned, then
why do doctors and pharmacists fail to inform their patients of those
risks?



That is a good question. Major journals and major medical associations
(eg, the AMA {American Medical Association}, ACOG {American College of
Obstetricians and Gynecologists}, and the AAP {American Academy of
Pediatrics}) have failed to stress or properly note this risk. Part of
the problem is that because the OCP/breast cancer debate is complicated,
most lay people have to rely on what "the experts" tell them.

A good example of this occurred recently in the Oxford study reported in
condensed version in The Lancet [257] and in complete form in
Contraception [258]. This study was and remains the largest
meta-analysis (ie, a synthesis of all the major studies done in a
particular field, concluding in an overall risk for the pooled studies)
regarding the studies of OCPs and breast cancer. Researchers from around
the world studied and combined the data from 54 studies, involving 25
countries and 53,297 women who had breast cancer. It concluded that:
"Women who are currently using combined oral contraceptives or have used
them in the past 10 years are at a slightly increased risk of having
breast cancer diagnosed, although the additional cancers tend to be
localized to the breast. There is no evidence of an increase in the risk
of having breast cancer diagnosed 10 or more years after cessation of
use...” Unfortunately, this study is known more for what it did say,
than what it did not say! There were several major weaknesses of the
study.

What are the weaknesses of the Oxford study and what implications do
they have?

The main weakness was the failure to report any evidence of what the
pooled risk of oral contraceptive use before a first term pregnancy was
in women less than 45 years old. Another major weakness is that the
Oxford study pooled data from studies which looked at women with breast
cancer from the early and mid 1970s [258, p56].

A woman's breast is especially sensitive to carcinogenic influence (ie,
cancer producing influence) before she has her first child since the
breast undergoes a maturing process throughout a woman's first
pregnancy. By failing to measure the effect of OCP use before a woman's
first term pregnancy (FTP), the Oxford study failed to give data on the
one group of women who are most likely to get breast cancer from oral
contraceptives, namely, those women who used them before their first
term pregnancy (eg, many teenagers and women in their twenties).

The second weakness is that the Oxford study used data from older
studies which took some of their data from the mid and early 1970s. This
does not leave a long enough latent period. A latent period is the time
between exposure to a suspected risk factor (eg, early OCP use) and the
cancer which it increases (eg, breast cancer). Often the latent period
between a risk factor and a cancer is 15 to 20 years or more (eg,
cigarettes and lung cancer). Although women in the US began taking OCPs
in the 1960s, they only began taking them for longer periods of time at
younger ages in the 1970s. Thus, only studies which include data from
the 1980s and 1990s or beyond would allow a long enough latent period to
pick up the influence of early OCP use.


OVERVIEW: BREAST CANCER AND THE PILL

Why is it important to study women who are under age 45?



Women who are under age 45 are more likely to have used OCPs prior to
having a child than women over 45. For example a 55-year old women who
had breast cancer in 1990 would have been very unlikely to have taken
the OCP for a significant period of time prior to giving birth since
OCPs were just coming to the US in the early 1960s when the cited woman
would have been in her late 20s.


What do the four largest studies, which take the bulk of their data
after 1980, state regarding women who used OCPs prior to first term
pregnancy (FTP)?


The table shows the results of the four largest studies which examined
women under age 45 and which took most of their data after 1980.

 

Table 2A: RISK OF BREAST CANCER IN WOMEN WITH OCP USE PRIOR TO FIRST
BIRTH

  AUTHOR YEARS STUDIED SIZE OF STUDY FINDINGS         Wingo [6] CASH
12/80-82 2089 less than age 45 40% INCREASE; AGES 20-44 Rosenberg [28A]
1977-1992 1427 less than age 45 88% INCREASE White [35] 1983-1990 747
less than age (Parous women) 50% INCREASE: FOR USE WITHIN 5 YEARS OF
MENARCHE Brinton [1] 5/90-12/92 1648 less than 45 years old 42%
INCREASED RISK*


*Computed from data from study, increase reflects the odds ratio

 

Has anyone done a meta-analysis of retrospective studies that examined
the question of risk in women under age 45 who had taken OCPs prior to
full term pregnancy?



Yes. Two different researchers have addressed this question. Thomas et
al, in 1991, found that women who took OCPs for extended periods of time
prior to FTP had a 42% increased risk [184]. A more refined
meta-analysis in 1990 by Romieu et al restricted her analysis to those
studies done after 1980. The study showed that women under age 45 who
had taken OCPs for four or more years prior to FTP had a 72% increased
incidence [RR=1.72 (1.36-2.19)] of breast cancer [55]

Can you comment on why a recent large study published by researchers at
Harvard claimed to show no increased risk of developing breast cancer in
women who had taken OCPs for five years or more prior to their first
term pregnancy?



In 1997, a group of researchers at Harvard Medical School led by Dr.
Hankinson published a study in Cancer Causes and Control [355]. It based
its conclusions on data taken from the Nurses' Health Study and claimed
to show that women who took oral contraceptive pills for five years or
more prior to their first term pregnancy had no increased risk of
developing breast cancer compared to women who never took OCPs (RR=0.57:
{0.24-1.31}). The study's conclusions appear to have been based on a
flawed analysis.

Can you describe the problems with the study?



Yes. The researchers compared women with breast cancer who took OCPs for
five years or more prior to first term pregnancy (FTP) [let's refer to
these women as Group A] to women with breast cancer who never took OCPs
[Group B].


It is known that women took OCPs for longer periods of time and earlier
in their reproductive lives in the 1980s and 1990s than in the 1960s and
1970s as was clearly noted in the Oxford study [258, p96; Tables 14,
15]. So any group of women who had taken OCPs for five years or more
prior to their FTP (ie, Group A) would have been more likely to have
done so while in their late teens and 20s in the 1980s or 1990s, while
women in Group B (who never took OCPs) would be more likely to contain a
distribution of women who would have been in their late teens and 20s in
either the 1960s, 1970s, 1980s or 1990s. But this strongly supports the
contention that women in Group A would have a lower average age and a
shorter follow-up time than the women in Group B, which would of course
invalidate the study's conclusions. **An example of a retrospective
study is one in which women with breast cancer would be interviewed and
asked questions about their risk factors such as family history, OCP
use, induced abortion, etc.

It is frightening to note that the Harvard team presented NO DATA on
either the average age of women in the noted groups or their respective
lengths of follow-up time. The research team instead chose to follow the
noted groups in "person-years" as their measure of follow-up time. This
is the length of a follow-up period derived from the number of women
followed, multiplied by the average number of years they were followed.
For example, if group A had 100 women who were followed for 10 years,
the total amount of follow-up time would be 100 x 10 = 1,000
"person-years". But if group A had 250 women who were followed for 4
years it would also have 1,000 "person-years" of follow-up. This is
totally inadequate since the measure of "person-years" gives no data on
the length of follow-up time in actual years and without this
information the study must remain suspect since it was noted that women
in group A most likely had both a younger average age and were followed
for a shorter period of time than the women in group B.

Is there any way that the public will ever have access to the necessary
data that was not presented in the Harvard study?



I am not sure. This author tried in vain to obtain the answers to three
basic questions over a six month period of time from three different
researchers involved in the Harvard study via e-mail, phone calls and
certified mail. It is ironic that one cannot access data from these
researchers especially since their study obtained its data from the
Nurses' Health Study, a study which was funded by our tax dollars
through a grant via the NCI (National Cancer Institute). The essential
questions that need to be answered are presented at the end of this
chapter. If the Harvard team had answered these questions the average
age and follow-up time period for both Group A and Group B's women could
have been easily calculated. Until the noted researchers at Harvard make
their data available for all to see, the study's conclusions must remain
suspect.

Have any other recent studies had methodological problems?



Yes, a large prospective study conducted in England by Beral et al [395]
claimed that a "cohort" (ie, the group being examined in a prospective
study) of 23,000 women who took the OCP had no greater risk of
developing breast cancer than 23,000 women who did not take the pill.
The main problem with the study is that women entered it from 1968 to
1969. But many of these women were taking the pill after they had a full
term pregnancy because as we noted earlier, women took OCPs for shorter
periods of time and later in their reproductive lives in the 1960s and
1970s than in the 1980s and 1990s [258]. The study's claim that OCP use
had no long-term risk of increasing breast cancer cannot be applied to
the subset of women who took (or currently take) OCPs for longer periods
of time prior to their first term pregnancy.

Can you give an overall statement regarding early OCP use and breast
cancer?



Yes. If a woman takes the oral contraceptive pill before her first child
is born, she suffers a 40% increased risk of developing breast cancer
compared to women who do not take the pill. If she takes OCPs for four
years or more prior to her first baby, she suffers at least a 72%
increased risk for developing breast cancer.

Are any other groups of women at high risk?



Yes. Women who take OCPs for long periods of time (ie, four years or
more) [8,26,34], are at increased risk for developing breast cancer.
Other women at risk are those who use them after age 25 [18,30,33] and
nulliparous women who use them for a long time (ie, four or more years)
[8,27]. All three categories of women seem to be at increased risk, with
individual studies ranging from 40% to over 200% increased risk. Women
who took OCPs for longer time periods and started using them at an early
age appear to be at an even greater risk. For example, the Brinton study
[1] is significant in that she allowed a longer latent period to pass
and found a 210% increased risk of developing breast cancer in young
women (ie, under age 35) who took OCPs for more than 10 years, if they
began taking them before age 18 [RR=3.1 (1.4-6.7)].

The studies you cited involved women who were less than 45 years old
from data taken after 1980. What will happen to the risk of developing
breast cancer for these women as they grow older?



No one knows. It would be wise to learn from history. In the late 1940s
an artificial female hormone named DES (Diethylstilbestrol) was given to
women to prevent miscarriages. For more than 25 years researchers
maintained that DES did not increase the risk of breast cancer in women
who took it. Finally, in the 1980s, it was discovered that DES increased
breast cancer by about 35%, especially in older women [85]. A similar
phenomenon may be occurring with OCPs. The truth is, no one knows how
dangerous OCPs will be in women as they grow older.

It has been noted that OCPs reduce the rate of uterine and ovarian
cancer. Is this true?



Yes, it is true. However it must be noted that OCPs also increase the
risk of cervical and liver cancer [215A, 215B, 264]. For example the
largest study to date, performed by the World Health Organization,
examined over 2,300 women and found that use of the pill before age 25
increased the risk of invasive cervical cancer by 45% [229D]. In
addition, more women get breast cancer in the US, than all of the other
alluded to cancers combined, making this the most dangerous risk in
western countries. Oral contraceptives may be particularly risky in
Asian and African countries where cervical and liver cancer are
prevalent [224B, 301].

Often women who have painful menstrual cycles are placed on OCPs. Are
there medical alternatives with less risks than the OCP?



Menstrual cramps can be controlled by other less harmful drugs called
non-steroidals such as naproxen or ibuprofen, alone, or in combination
with acetominophen.* Other doctors treat cramps by encouraging women to
take 1,000 mg of calcium and the RDA (recommended daily allowance) of
magnesium directly before and during menstruation. Conversely, The
Journal of Adolescent Medicine published a case report of a young lady
who experienced a 90% reduction in her cramping symptoms when taking
nicardipine for relief of her menstrual cramps [344]. Nicardipine is a
type of calcium channel blocker that is used for treating hypertension.

What about the risk of "low dose" progestin containing contraceptives
such as "the minipill," or long-acting progestins such as Norplant or
Depo-Provera?



Skegg et al [163] pooled the data from the World Health Organization
(WHO) and New Zealand studies, the two largest studies that looked at
women who took Depo-Provera (active ingredient is DMPA:
depot-medroxyprogesterone acetate) for long periods of time. He found
that women who had taken DMPA for between two and three years before age
25 had a 310% statistically significant risk of getting breast cancer
{RR=4.1: (1.6-10.90} while women who had taken DMPA for more than 3
years prior to age 25 had at least a 190% increased risk, that was also
significant {RR=2.9: (1.2-7.1)}. The risks for long-term Norplant use in
young women could be just as high as for Depo-Provera users, although
widespread tests have not been done because Norplant was developed later
than Depo-Provera. In regard to the progestin containing "minipill," the
Oxford study noted an overall increased risk of 19% (ie, 1.19
[0.89-1.49]) in women who had taken minipills for four or more years,
but they said nothing about extended use in young women, especially
women who took them prior to first term pregnancy [258, p986]. The
latter group of women might be at an especially increased risk.

How do the natural means of regulating birth compare to the artificial
means?



Several well-designed trials by the World Health Organization have shown
that Natural Family Planning (NFP) (ie, a method for determining when a
woman is most fertile or infertile, based on qualitative observations of
cervical mucus and, for some NFP users, measuring basal body
temperature) has had an effectiveness rate when used correctly that is
better than OCPs, that is, less than 3% pregnancies per year. These
trials have been done in both modern and less advanced countries and
have shown low annual pregnancy rates: the United Kingdom -- 2.7% [280],
Germany -- 2.3% [281], Belgium -- 1.7% [282] , and India -- 2.0% [283].
One of the largest trials (of 19,843 women performed by the World Health
Organization in India) showed the failure rate to be 0.2 pregnancies per
100 women yearly -- a rate that is significantly better than almost all
artificial methods of contraception [286]. (For more information
regarding NFP see end of bibliography).

How can I verify the above noted information?



Go to your nearest medical library -- nearly every hospital has one --
and ask the librarian to help you look up the medical references that
interest you.


*The non-steroidals may have to be taken in higher doses to be effective
and should then be used only under a physician's guidance.

The researchers at Harvard have never answered the following simple
questions:


1) How many women were there in the group who were under age 45 and who
used oral contraceptives for 5 years or more prior to first full term
pregnancy (see page 69, Table 3 of your paper {ie, the women who were
followed for 9,741 person-years}). What was the mean age for the women
in this group?

2) How many women were there in the group who were under age 45 and
never used the pill? [see Table 2 page 68, these women were followed for
176,306 person-years]. What was their mean age?

3) How many women were in the group who were under age 45 and had used
the pill for 10 years or more of total duration? (Correlating to Table 2
on page 68, the group that had 21,760 person-years of follow-up)

OVERVIEW: BREAST CANCER AND THE PILL

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355 Hankinson SE et al. A prospective study of oral contraceptive use
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Causes and Control. 1997; 8: 65-72.

229D Thomas DB et al. Invasive squamos-cell cervical carcinoma and
combined oral contraceptives: Results from a multinational study. Int. J
of Cancer. 1993. 53; 228-236.

For more information on NFP call or write to:


* The Couple to Couple League PO Box 111184 Cincinnati, Ohio 45211-1184
1-513-661-7612 * Pope Paul VI Institute at 1-402-390-6600 * Family of
the Americas 1-800-443-3395 www.familyplanning.net; e-mail;
family@upbeat.com * Billings Ovulation Method Association

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