Calling all Stage II Sisters!!!

CP418 and Sanbar...and everyone else who are interested in birth control and cancer...please read Malcolm Gladwell's John Rock's Error.  I know it's a very long article...but it's worth reading...twice!

John Rock's Error

March 10, 2000
ANNALS OF MEDICINE

What the co-inventor of the Pill
didn't know about
menstruation
can endanger women's health.

1.

John Rock was christened in 1890 at the Church of the Immaculate
Conception in Marlborough, Massachusetts, and married by Cardinal William
O'Connell, of Boston. He had five children and nineteen grandchildren. A
crucifix hung above his desk, and nearly every day of his adult life he attended
the 7 a.m. Mass at St. Mary's in Brookline. Rock, his friends would say, was in
love with his church. He was also one of the inventors of the birth-control
pill, and it was his conviction that his faith and his vocation were perfectly
compatible. To anyone who disagreed he would simply repeat the words spoken to
him as a child by his home-town priest: "John, always stick to your conscience.
Never let anyone else keep it for you. And I mean anyone else." Even when
Monsignor Francis W. Carney, of Cleveland, called him a "moral rapist," and when
Frederick Good, the longtime head of obstetrics at Boston City Hospital, went to
Boston's Cardinal Richard Cushing to have Rock excommunicated, Rock was unmoved.
"You should be afraid to meet your Maker," one angry woman wrote to him, soon
after the Pill was approved. "My dear madam," Rock wrote back, "in my faith, we
are taught that the Lord is with us always. When my time comes, there will be no
need for introductions."

In the years immediately after the Pill was approved by the
F.D.A., in 1960, Rock was everywhere. He appeared in interviews and
documentaries on CBS and NBC, in Time, Newsweek, Life, The Saturday
Evening Post. He toured the country tirelessly. He wrote a widely discussed
book, "The Time Has Come: A Catholic Doctor's Proposals to End the Battle Over
Birth Control," which was translated into French, German, and Dutch. Rock was
six feet three and rail-thin, with impeccable manners; he held doors open for
his patients and addressed them as "Mrs." or "Miss." His mere association with
the Pill helped make it seem respectable. "He was a man of great dignity," Dr.
Sheldon J. Segal, of the Population Council, recalls. "Even if the occasion
called for an open collar, you'd never find him without an ascot. He had the
shock of white hair to go along with that. And posture, straight as an arrow,
even to his last year." At Harvard Medical School, he was a giant, teaching
obstetrics for more than three decades. He was a pioneer in in-vitro
fertilization and the freezing of sperm cells, and was the first to extract an
intact fertilized egg. The Pill was his crowning achievement. His two
collaborators, Gregory Pincus and Min- Cheuh Chang, worked out the mechanism. He
shepherded the drug through its clinical trials. "It was his name and his
reputation that gave ultimate validity to the claims that the pill would protect
women against unwanted pregnancy," Loretta McLaughlin writes in her marvellous
1982 biography of Rock. Not long before the Pill's approval, Rock travelled to
Washington to testify before the F.D.A. about the drug's safety. The agency
examiner, Pasquale DeFelice, was a Catholic obstetrician from Georgetown
University, and at one point, the story goes, DeFelice suggested the
unthinkable--that the Catholic Church would never approve of the birth-control
pill. "I can still see Rock standing there, his face composed, his eyes riveted
on DeFelice," a colleague recalled years later, "and then, in a voice that would
congeal your soul, he said, 'Young man, don't you sell my church short.'
"

In the end, of course, John Rock's church disappointed him. In
1968, in the encyclical "Humanae Vitae," Pope Paul VI outlawed oral
contraceptives and all other "artificial" methods of birth control. The passion
and urgency that animated the birth-control debates of the sixties are now a
memory. John Rock still matters, though, for the simple reason that in the
course of reconciling his church and his work he made an error. It was not a
deliberate error. It became manifest only after his death, and through
scientific advances he could not have anticipated. But because that mistake
shaped the way he thought about the Pill--about what it was, and how it worked,
and most of all what it meant--and because John Rock was one of those
responsible for the way the Pill came into the world, his error has colored the
way people have thought about contraception ever since.

John Rock believed that the Pill was a "natural" method of birth
control. By that he didn't mean that it felt natural, because it
obviously didn't for many women, particularly not in its earliest days, when the
doses of hormone were many times as high as they are today. He meant that it
worked by natural means. Women can get pregnant only during a certain interval
each month, because after ovulation their bodies produce a surge of the hormone
progesterone. Progesterone--one of a class of hormones known as
progestin--prepares the uterus for implantation and stops the ovaries from
releasing new eggs; it favors gestation. "It is progesterone, in the healthy
woman, that prevents ovulation and establishes the pre- and post-menstrual
'safe' period," Rock wrote. When a woman is pregnant, her body produces a stream
of progestin in part for the same reason, so that another egg can't be released
and threaten the pregnancy already under way. Progestin, in other words, is
nature's contraceptive. And what was the Pill? Progestin in tablet form. When a
woman was on the Pill, of course, these hormones weren't coming in a sudden
surge after ovulation and weren't limited to certain times in her cycle. They
were being given in a steady dose, so that ovulation was permanently shut down.
They were also being given with an additional dose of estrogen, which holds the
endometrium together and--as we've come to learn--helps maintain other tissues
as well. But to Rock, the timing and combination of hormones wasn't the issue.
The key fact was that the Pill's ingredients duplicated what could be found in
the body naturally. And in that naturalness he saw enormous theological
significance.

In 1951, for example, Pope Pius XII had sanctioned the rhythm
method for Catholics because he deemed it a "natural" method of regulating
procreation: it didn't kill the sperm, like a spermicide, or frustrate the
normal process of procreation, like a diaphragm, or mutilate the organs, like
sterilization. Rock knew all about the rhythm method. In the nineteen-thirties,
at the Free Hospital for Women, in Brookline, he had started the country's first
rhythm clinic for educating Catholic couples in natural contraception. But how
did the rhythm method work? It worked by limiting sex to the safe period that
progestin created. And how did the Pill work? It worked by using progestin to
extend the safe period to the entire month. It didn't mutilate the reproductive
organs, or damage any natural process. "Indeed," Rock wrote, oral contraceptives
"may be characterized as a 'pill-established safe period,' and would seem to
carry the same moral implications" as the rhythm method. The Pill was, to Rock,
no more than "an adjunct to nature."

In 1958, Pope Pius XII approved the Pill for Catholics, so long as
its contraceptive effects were "indirect"--that is, so long as it was intended
only as a remedy for conditions like painful menses or "a disease of the
uterus." That ruling emboldened Rock still further. Short-term use of the Pill,
he knew, could regulate the cycle of women whose periods had previously been
unpredictable. Since a regular menstrual cycle was necessary for the successful
use of the rhythm method--and since the rhythm method was sanctioned by the
Church--shouldn't it be permissible for women with an irregular menstrual cycle
to use the Pill in order to facilitate the use of rhythm? And if that was true
why not take the logic one step further? As the federal judge John T. Noonan
writes in "Contraception," his history of the Catholic position on birth
control:

If it was lawful to suppress ovulation to achieve a regularity
necessary for successfully sterile intercourse, why was it not lawful to
suppress ovulation without appeal to rhythm? If pregnancy could be prevented by
pill plus rhythm, why not by pill alone? In each case suppression of ovulation
was used as a means. How was a moral difference made by the addition of
rhythm?

These arguments, as arcane as they may seem, were central to the
development of oral contraception. It was John Rock and Gregory Pincus who
decided that the Pill ought to be taken over a four-week cycle--a woman would
spend three weeks on the Pill and the fourth week off the drug (or on a
placebo), to allow for menstruation. There was and is no medical reason for
this. A typical woman of childbearing age has a menstrual cycle of around
twenty- eight days, determined by the cascades of hormones released by her
ovaries. As first estrogen and then a combination of estrogen and progestin
flood the uterus, its lining becomes thick and swollen, preparing for the
implantation of a fertilized egg. If the egg is not fertilized, hormone levels
plunge and cause the lining--the endometrium--to be sloughed off in a menstrual
bleed. When a woman is on the Pill, however, no egg is released, because the
Pill suppresses ovulation. The fluxes of estrogen and progestin that cause the
lining of the uterus to grow are dramatically reduced, because the Pill slows
down the ovaries. Pincus and Rock knew that the effect of the Pill's hormones on
the endometrium was so modest that women could conceivably go for months without
having to menstruate. "In view of the ability of this compound to prevent
menstrual bleeding as long as it is taken," Pincus acknowledged in 1958, "a
cycle of any desired length could presumably be produced." But he and Rock
decided to cut the hormones off after three weeks and trigger a menstrual period
because they believed that women would find the continuation of their monthly
bleeding reassuring. More to the point, if Rock wanted to demonstrate that the
Pill was no more than a natural variant of the rhythm method, he couldn't very
well do away with the monthly menses. Rhythm required "regularity," and so the
Pill had to produce regularity as well.

It has often been said of the Pill that no other drug has ever
been so instantly recognizable by its packaging: that small, round plastic dial
pack. But what was the dial pack if not the physical embodiment of the
twenty-eight-day cycle? It was, in the words of its inventor, meant to fit into
a case "indistinguishable" from a woman's cosmetics compact, so that it might be
carried "without giving a visual clue as to matters which are of no concern to
others." Today, the Pill is still often sold in dial packs and taken in
twenty-eight-day cycles. It remains, in other words, a drug shaped by the
dictates of the Catholic Church--by John Rock's desire to make this new method
of birth control seem as natural as possible. This was John Rock's error. He was
consumed by the idea of the natural. But what he thought was natural wasn't so
natural after all, and the Pill he ushered into the world turned out to be
something other than what he thought it was. In John Rock's mind the dictates of
religion and the principles of science got mixed up, and only now are we
beginning to untangle them.

2.

In 1986, a young scientist named Beverly Strassmann travelled to
Africa to live with the Dogon tribe of Mali. Her research site was the village
of Sangui in the Sahel, about a hundred and twenty miles south of Timbuktu. The
Sahel is thorn savannah, green in the rainy season and semi-arid the rest of the
year. The Dogon grow millet, sorghum, and onions, raise livestock, and live in
adobe houses on the Bandiagara escarpment. They use no contraception. Many of
them have held on to their ancestral customs and religious beliefs. Dogon
farmers, in many respects, live much as people of that region have lived since
antiquity. Strassmann wanted to construct a precise reproductive profile of the
women in the tribe, in order to understand what female biology might have been
like in the millennia that preceded the modern age. In a way, Strassmann was
trying to answer the same question about female biology that John Rock and the
Catholic Church had struggled with in the early sixties: what is natural? Only,
her sense of "natural" was not theological but evolutionary. In the era during
which natural selection established the basic patterns of human biology--the
natural history of our species--how often did women have children? How often did
they menstruate? When did they reach puberty and menopause? What impact did
breast-feeding have on ovulation? These questions had been studied before, but
never so thoroughly that anthropologists felt they knew the answers with any
certainty.

Strassmann, who teaches at the University of Michigan at Ann
Arbor, is a slender, soft-spoken woman with red hair, and she recalls her time
in Mali with a certain wry humor. The house she stayed in while in Sangui had
been used as a shelter for sheep before she came and was turned into a pigsty
after she left. A small brown snake lived in her latrine, and would curl up in a
camouflaged coil on the seat she sat on while bathing. The villagers, she says,
were of two minds: was it a deadly snake--Kere me jongolo,
literally, "My bite cannot be healed"--or a harmless mouse snake? (It turned out
to be the latter.) Once, one of her neighbors and best friends in the tribe
roasted her a rat as a special treat. "I told him that white people aren't
allowed to eat rat because rat is our totem," Strassmann says. "I can still see
it. Bloated and charred. Stretched by its paws. Whiskers singed. To say nothing
of the tail." Strassmann meant to live in Sangui for eighteen months, but her
experiences there were so profound and exhilarating that she stayed for two and
a half years. "I felt incredibly privileged," she says. "I just couldn't tear
myself away."

Part of Strassmann's work focussed on the Dogon's practice of
segregating menstruating women in special huts on the fringes of the village. In
Sangui, there were two menstrual huts--dark, cramped, one-room adobe structures,
with boards for beds. Each accommodated three women, and when the rooms were
full, latecomers were forced to stay outside on the rocks. "It's not a place
where people kick back and enjoy themselves," Strassmann says. "It's simply a
nighttime hangout. They get there at dusk, and get up early in the morning and
draw their water." Strassmann took urine samples from the women using the hut,
to confirm that they were menstruating. Then she made a list of all the women in
the village, and for her entire time in Mali--seven hundred and thirty- six
consecutive nights--she kept track of everyone who visited the hut. Among the
Dogon, she found, a woman, on average, has her first period at the age of
sixteen and gives birth eight or nine times. From menarche, the onset of
menstruation, to the age of twenty, she averages seven periods a year. Over the
next decade and a half, from the age of twenty to the age of thirty-four, she
spends so much time either pregnant or breast-feeding (which, among the Dogon,
suppresses ovulation for an average of twenty months) that she averages only
slightly more than one period per year. Then, from the age of thirty-five until
menopause, at around fifty, as her fertility rapidly declines, she averages four
menses a year. All told, Dogon women menstruate about a hundred times in their
lives. (Those who survive early childhood typically live into their seventh or
eighth decade.) By contrast, the average for contemporary Western women is
somewhere between three hundred and fifty and four hundred times.

Strassmann's office is in the basement of a converted stable next
to the Natural History Museum on the University of Michigan campus. Behind her
desk is a row of battered filing cabinets, and as she was talking she turned and
pulled out a series of yellowed charts. Each page listed, on the left, the first
names and identification numbers of the Sangui women. Across the top was a time
line, broken into thirty-day blocks. Every menses of every woman was marked with
an X. In the village, Strassmann explained, there were two women who were
sterile, and, because they couldn't get pregnant, they were regulars at the
menstrual hut. She flipped through the pages until she found them. "Look, she
had twenty-nine menses over two years, and the other had twenty- three." Next to
each of their names was a solid line of x's. "Here's a woman approaching
menopause," Strassmann went on, running her finger down the page. "She's cycling
but is a little bit erratic. Here's another woman of prime childbearing age. Two
periods. Then pregnant. I never saw her again at the menstrual hut. This woman
here didn't go to the menstrual hut for twenty months after giving birth,
because she was breast-feeding. Two periods. Got pregnant. Then she miscarried,
had a few periods, then got pregnant again. This woman had three menses in the
study period." There weren't a lot of x's on Strassmann's sheets. Most of the
boxes were blank. She flipped back through her sheets to the two anomalous women
who were menstruating every month. "If this were a menstrual chart of
undergraduates here at the University of Michigan, all the rows would be like
this."

Strassmann does not claim that her statistics apply to every
preindustrial society. But she believes--and other anthropological work backs
her up--that the number of lifetime menses isn't greatly affected by differences
in diet or climate or method of subsistence (foraging versus agriculture, say).
The more significant factors, Strassmann says, are things like the prevalence of
wet-nursing or sterility. But over all she believes that the basic pattern of
late menarche, many pregnancies, and long menstrual-free stretches caused by
intensive breast-feeding was virtually universal up until the "demographic
transition" of a hundred years ago from high to low fertility. In other words,
what we think of as normal--frequent menses--is in evolutionary terms abnormal.
"It's a pity that gynecologists think that women have to menstruate every
month,"Strassmann went on. "They just don't understand the real biology of
menstruation."

To Strassmann and others in the field of evolutionary medicine,
this shift from a hundred to four hundred lifetime menses is enormously
significant. It means that women's bodies are being subjected to changes and
stresses that they were not necessarily designed by evolution to handle. In a
brilliant and provocative book, "Is Menstruation Obsolete?," Drs. Elsimar
Coutinho and Sheldon S. Segal, two of the world's most prominent contraceptive
researchers, argue that this recent move to what they call "incessant ovulation"
has become a serious problem for women's health. It doesn't mean that women are
always better off the less they menstruate. There are times--particularly in the
context of certain medical conditions--when women ought to be concerned if they
aren't menstruating: In obese women, a failure to menstruate can signal an
increased risk of uterine cancer. In female athletes, a failure to menstruate
can signal an increased risk of osteoporosis. But for most women, Coutinho and
Segal say, incessant ovulation serves no purpose except to increase the
occurence of abdominal pain, mood shifts, migraines, endometriosis, fibroids,
and anemia--the last of which, they point out, is "one of the most serious
health problems in the world."

Most serious of all is the greatly increased risk of some cancers.
Cancer, after all, occurs because as cells divide and reproduce they sometimes
make mistakes that cripple the cells' defenses against runaway growth. That's
one of the reasons that our risk of cancer generally increases as we age: our
cells have more time to make mistakes. But this also means that any
change promoting cell division has the potential to increase cancer risk, and
ovulation appears to be one of those changes. Whenever a woman ovulates, an egg
literally bursts through the walls of her ovaries. To heal that puncture, the
cells of the ovary wall have to divide and reproduce. Every time a woman gets
pregnant and bears a child, her lifetime risk of ovarian cancer drops ten per
cent. Why? Possibly because, between nine months of pregnancy and the
suppression of ovulation associated with breast-feeding, she stops ovulating for
twelve months--and saves her ovarian walls from twelve bouts of cell division.
The argument is similar for endometrial cancer. When a woman is menstruating,
the estrogen that flows through her uterus stimulates the growth of the uterine
lining, causing a flurry of potentially dangerous cell division. Women who do
not menstruate frequently spare the endometrium that risk. Ovarian and
endometrial cancer are characteristically modern diseases, consequences, in
part, of a century in which women have come to menstruate four hundred times in
a lifetime.

In this sense, the Pill really does have a "natural"effect. By
blocking the release of new eggs, the progestin in oral contraceptives reduces
the rounds of ovarian cell division. Progestin also counters the surges of
estrogen in the endometrium, restraining cell division there. A woman who takes
the Pill for ten years cuts her ovarian-cancer risk by around seventy per cent
and her endometrial-cancer risk by around sixty per cent. But here "natural"
means something different from what Rock meant. He assumed that the Pill was
natural because it was an unobtrusive variant of the body's own processes. In
fact, as more recent research suggests, the Pill is really only natural in so
far as it's radical--rescuing the ovaries and endometrium from modernity.
That Rock insisted on a twenty-eight-day cycle for his pill is evidence of just
how deep his misunderstanding was: the real promise of the Pill was not that it
could preserve the menstrual rhythms of the twentieth century but that it could
disrupt them.

Today, a growing movement of reproductive specialists has begun to
campaign loudly against the standard twenty-eight-day pill regimen. The drug
company Organon has come out with a new oral contraceptive, called Mircette,
that cuts the seven-day placebo interval to two days. Patricia Sulak, a medical
researcher at Texas A.& M. University, has shown that most women can
probably stay on the Pill, straight through, for six to twelve weeks before they
experience breakthrough bleeding or spotting. More recently, Sulak has
documented precisely what the cost of the Pill's monthly "off" week is. In a
paper in the February issue of the journal Obstetrics and
Gynecology, she and her colleagues documented something that will come as no
surprise to most women on the Pill: during the placebo week, the number of users
experiencing pelvic pain, bloating, and swelling more than triples, breast
tenderness more than doubles, and headaches increase by almost fifty per cent.
In other words, some women on the Pill continue to experience the kinds of side
effects associated with normal menstruation. Sulak's paper is a short, dry,
academic work, of the sort intended for a narrow professional audience. But it
is impossible to read it without being struck by the consequences of John Rock's
desire to please his church. In the past forty years, millions of women around
the world have been given the Pill in such a way as to maximize their pain and
suffering. And to what end? To pretend that the Pill was no more than a
pharmaceutical version of the rhythm method?

3.

In 1980 and 1981, Malcolm Pike, a medical statistician at the
University of Southern California, travelled to Japan for six months to study at
the Atomic Bomb Casualties Commission. Pike wasn't interested in the effects of
the bomb. He wanted to examine the medical records that the commission had been
painstakingly assembling on the survivors of Hiroshima and Nagasaki. He was
investigating a question that would ultimately do as much to complicate our
understanding of the Pill as Strassmann's research would a decade later: why did
Japanese women have breast-cancer rates six times lower than American women?

In the late forties, the World Health Organization began to
collect and publish comparative health statistics from around the world, and the
breast-cancer disparity between Japan and America had come to obsess cancer
specialists. The obvious answer--that Japanese women were somehow genetically
protected against breast cancer--didn't make sense, because once Japanese women
moved to the United States they began to get breast cancer almost as often as
American women did. As a result, many experts at the time assumed that the
culprit had to be some unknown toxic chemical or virus unique to the West. Brian
Henderson, a colleague of Pike's at U.S.C. and his regular collaborator, says
that when he entered the field, in 1970, "the whole viral- and chemical-
carcinogenesis idea was huge--it dominated the literature." As he recalls,
"Breast cancer fell into this large, unknown box that said it was something to
do with the environment--and that word 'environment' meant a lot of different
things to a lot of different people. They might be talking about diet or smoking
or pesticides."

Henderson and Pike, however, became fascinated by a number of
statistical pecularities. For one thing, the rate of increase in breast-cancer
risk rises sharply throughout women's thirties and forties and then, at
menopause, it starts to slow down. If a cancer is caused by some toxic outside
agent, you'd expect that rate to rise steadily with each advancing year, as the
number of mutations and genetic mistakes steadily accumulates. Breast cancer, by
contrast, looked as if it were being driven by something specific to a woman's
reproductive years. What was more, younger women who had had their ovaries
removed had a markedly lower risk of breast cancer; when their bodies weren't
producing estrogen and progestin every month, they got far fewer tumors. Pike
and Henderson became convinced that breast cancer was linked to a process of
cell division similar to that of ovarian and endometrial cancer. The female
breast, after all, is just as sensitive to the level of hormones in a woman's
body as the reproductive system. When the breast is exposed to estrogen, the
cells of the terminal-duct lobular unit--where most breast cancer
arises--undergo a flurry of division. And during the mid-to-late stage of the
menstrual cycle, when the ovaries start producing large amounts of progestin,
the pace of cell division in that region doubles.

It made intuitive sense, then, that a woman's risk of breast
cancer would be linked to the amount of estrogen and progestin her breasts have
been exposed to during her lifetime. How old a woman is at menarche should make
a big difference, because the beginning of puberty results in a hormonal surge
through a woman's body, and the breast cells of an adolescent appear to be
highly susceptible to the errors that result in cancer. (For more complicated
reasons, bearing children turns out to be protective against breast cancer,
perhaps because in the last two trimesters of pregnancy the cells of the breast
mature and become much more resistant to mutations.) How old a woman is at
menopause should matter, and so should how much estrogen and progestin her
ovaries actually produce, and even how much she weighs after menopause, because
fat cells turn other hormones into estrogen.

Pike went to Hiroshima to test the cell-division theory. With
other researchers at the medical archive, he looked first at the age when
Japanese women got their period. A Japanese woman born at the turn of the
century had her first period at sixteen and a half. American women born at the
same time had their first period at fourteen. That difference alone, by their
calculation, was sufficient to explain forty per cent of the gap between
American and Japanese breast-cancer rates. "They had collected amazing records
from the women of that area," Pike said. "You could follow precisely the change
in age of menarche over the century. You could even see the effects of the
Second World War. The age of menarche of Japanese girls went up right at that
point because of poor nutrition and other hardships. And then it started to go
back down after the war. That's what convinced me that the data were
wonderful."

Pike, Henderson, and their colleagues then folded in the other
risk factors. Age at menopause, age at first pregnancy, and number of children
weren't sufficiently different between the two countries to matter. But weight
was. The average post- menopausal Japanese woman weighed a hundred pounds; the
average American woman weighed a hundred and forty-five pounds. That fact
explained another twenty-five per cent of the difference. Finally, the
researchers analyzed blood samples from women in rural Japan and China, and
found that their ovaries-- possibly because of their extremely low-fat
diet--were producing about seventy-five per cent the amount of estrogen that
American women were producing. Those three factors, added together, seemed to
explain the breast-cancer gap. They also appeared to explain why the rates of
breast cancer among Asian women began to increase when they came to America: on
an American diet, they started to menstruate earlier, gained more weight, and
produced more estrogen. The talk of chemicals and toxins and power lines and
smog was set aside. "When people say that what we understand about breast cancer
explains only a small amount of the problem, that it is somehow a mystery, it's
absolute nonsense," Pike says flatly. He is a South African in his sixties, with
graying hair and a salt-and-pepper beard. Along with Henderson, he is an eminent
figure in cancer research, but no one would ever accuse him of being tentative
in his pronouncements. "We understand breast cancer extraordinarily well. We
understand it as well as we understand cigarettes and lung cancer."

What Pike discovered in Japan led him to think about the Pill,
because a tablet that suppressed ovulation--and the monthly tides of estrogen
and progestin that come with it--obviously had the potential to be a powerful
anti-breast-cancer drug. But the breast was a little different from the
reproductive organs. Progestin prevented ovarian cancer because it suppressed
ovulation. It was good for preventing endometrial cancer because it countered
the stimulating effects of estrogen. But in breast cells, Pike believed,
progestin wasn't the solution; it was one of the hormones that caused
cell division. This is one explanation for why, after years of studying the
Pill, researchers have concluded that it has no effect one way or the other on
breast cancer: whatever beneficial effect results from what the Pill does is
cancelled out by how it does it. John Rock touted the fact that the Pill used
progestin, because progestin was the body's own contraceptive. But Pike saw
nothing "natural"about subjecting the breast to that heavy a dose of proges-
tin. In his view, the amount of progestin and estrogen needed to make an
effective contraceptive was much greater than the amount needed to keep the
reproductive system healthy--and that excess was unnecessarily raising the risk
of breast cancer. A truly natural Pill might be one that found a way to suppress
ovulation without using progestin. Throughout the nineteen-eighties, Pike
recalls, this was his obsession. "We were all trying to work out how the hell we
could fix the Pill. We thought about it day and night."

4.

Pike's proposed solution is a class of drugs known as GnRHAs,
which has been around for many years. GnRHAs disrupt the signals that the
pituitary gland sends when it is attempting to order the manufacture of sex
hormones. It's a circuit breaker. "We've got substantial experience with this
drug," Pike says. Men suffering from prostate cancer are sometimes given a GnRHA
to temporarily halt the production of testosterone, which can exacerbate their
tumors. Girls suffering from what's called precocious puberty--puberty at seven
or eight, or even younger--are sometimes given the drug to forestall sexual
maturity. If you give GnRHA to women of childbearing age, it stops their ovaries
from producing estrogen and progestin. If the conventional Pill works by
convincing the body that it is, well, a little bit pregnant, Pike's pill would
work by convincing the body that it was menopausal.

In the form Pike wants to use it, GnRHA will come in a clear glass
bottle the size of a saltshaker, with a white plastic mister on top. It will be
inhaled nasally. It breaks down in the body very quickly. A morning dose simply
makes a woman menopausal for a while. Menopause, of course, has its risks. Women
need estrogen to keep their hearts and bones strong. They also need progestin to
keep the uterus healthy. So Pike intends to add back just enough of each hormone
to solve these problems, but much less than women now receive on the Pill.
Ideally, Pike says, the estrogen dose would be adjustable: women would try
various levels until they found one that suited them. The progestin would come
in four twelve-day stretches a year. When someone on Pike's regimen stopped the
progestin, she would have one of four annual menses.

Pike and an oncologist named Darcy Spicer have joined forces with
another oncologist, John Daniels, in a startup called Balance Pharmaceuticals.
The firm operates out of a small white industrial strip mall next to the freeway
in Santa Monica. One of the tenants is a paint store, another looks like some
sort of export company. Balance's offices are housed in an oversized garage with
a big overhead door and concrete floors. There is a tiny reception area, a
little coffee table and a couch, and a warren of desks, bookshelves, filing
cabinets, and computers. Balance is testing its formulation on a small group of
women at high risk for breast cancer, and if the results continue to be
encouraging, it will one day file for F.D.A. approval.

"When I met Darcy Spicer a couple of years ago," Pike said
recently, as he sat at a conference table deep in the Balance garage, "he said,
'Why don't we just try it out? By taking mammograms, we should be able to see
changes in the breasts of women on this drug, even if we add back a little
estrogen to avoid side effects.' So we did a study, and we found that there were
huge changes." Pike pulled out a paper he and Spicer had published in the
Journal of the National Cancer Institute, showing breast X-rays of
three young women. "These are the mammograms of the women before they start," he
said. Amid the grainy black outlines of the breast were large white fibrous
clumps--clumps that Pike and Spicer believe are indicators of the kind of
relentless cell division that increases breast-cancer risk. Next to those x-rays
were three mammograms of the same women taken after a year on the GnRHA regimen.
The clumps were almost entirely gone. "This to us represents that we have
actually stopped the activity inside the breasts," Pike went on. "White is a
proxy for cell proliferation. We're slowing down the breast."

Pike stood up from the table and turned to a sketch pad on an
easel behind him. He quickly wrote a series of numbers on the paper. "Suppose a
woman reaches menarche at fifteen and menopause at fifty. That's thirty-five
years of stimulating the breast. If you cut that time in half, you will change
her risk not by half but by half raised to the power of 4.5." He was working
with a statistical model he had developed to calculate breast-cancer risk.
"That's one-twenty-third. Your risk of breast cancer will be one- twenty-third
of what it would be otherwise. It won't be zero. You can't get to zero. If you
use this for ten years, your risk will be cut by at least half. If you use it
for five years, your risk will be cut by at least a third. It's as if your
breast were to be five years younger, or ten years younger--forever." The
regimen, he says, should also provide protection against ovarian cancer.

Pike gave the sense that he had made this little speech many times
before, to colleagues, to his family and friends--and to investors. He knew by
now how strange and unbelievable what he was saying sounded. Here he was, in a
cold, cramped garage in the industrial section of Santa Monica, arguing that he
knew how to save the lives of hundreds of thousands of women around the world.
And he wanted to do that by making young women menopausal through a chemical
regimen sniffed every morning out of a bottle. This was, to say the least, a
bold idea. Could he strike the right balance between the hormone levels women
need to stay healthy and those that ultimately make them sick? Was progestin
really so important in breast cancer? There are cancer specialists who remain
skeptical. And, most of all, what would women think? John Rock, at least, had
lent the cause of birth control his Old World manners and distinguished white
hair and appeals from theology; he took pains to make the Pill seem like the
least radical of interventions--nature's contraceptive, something that could be
slipped inside a woman's purse and pass without notice. Pike was going to take
the whole forty-year mythology of "natural" and sweep it aside. "Women are going
to think, I'm being manipulated here. And it's a perfectly reasonable thing to
think." Pike's South African accent gets a little stronger as he becomes more
animated. "But the modern way of living represents an extraordinary change in
female biology. Women are going out and becoming lawyers, doctors, presidents of
countries. They need to understand that what we are trying to do isn't abnormal.
It's just as normal as when someone hundreds of years ago had menarche at
seventeen and had five babies and had three hundred fewer menstrual cycles than
most women have today. The world is not the world it was. And some of the risks
that go with the benefits of a woman getting educated and not getting pregnant
all the time are breast cancer and ovarian cancer, and we need to deal with it.
I have three daughters. The earliest grandchild I had was when one of them was
thirty-one. That's the way many women are now. They ovulate from twelve or
thirteen until their early thirties. Twenty years of uninterrupted ovulation
before their first child! That's a brand-new phenomenon!"

5.

John Rock's long battle on behalf of his birth-control pill forced
the Church to take notice. In the spring of 1963, just after Rock's book was
published, a meeting was held at the Vatican between high officials of the
Catholic Church and Donald B. Straus, the chairman of Planned Parenthood. That
summit was followed by another, on the campus of the University of Notre Dame.
In the summer of 1964, on the eve of the feast of St. John the Baptist, Pope
Paul VI announced that he would ask a committee of church officials to reëxamine
the Vatican's position on contraception. The group met first at the Collegio San
Jose, in Rome, and it was clear that a majority of the committee were in favor
of approving the Pill. Committee reports leaked to the National Catholic
Register confirmed that Rock's case appeared to be winning. Rock was elated.
Newsweek put him on its cover, and ran a picture of the Pope inside. "Not
since the Copernicans suggested in the sixteenth century that the sun was the
center of the planetary system has the Roman Catholic Church found itself on
such a perilous collision course with a new body of knowledge," the article
concluded. Paul VI, however, was unmoved. He stalled, delaying a verdict for
months, and then years. Some said he fell under the sway of conservative
elements within the Vatican. In the interim, theologians began exposing the
holes in Rock's arguments. The rhythm method " 'prevents' conception by
abstinence, that is, by the non-performance of the conjugal act during the
fertile period," the Catholic journal America concluded in a 1964
editorial. "The pill prevents conception by suppressing ovulation and by thus
abolishing the fertile period. No amount of word juggling can make abstinence
from sexual relations and the suppression of ovulation one and the same thing."
On July 29, 1968, in the "Humanae Vitae" encyclical, the Pope broke his silence,
declaring all "artificial" methods of contraception to be against the teachings
of the Church.

In hindsight, it is possible to see the opportunity that Rock
missed. If he had known what we know now and had talked about the Pill not as a
contraceptive but as a cancer drug--not as a drug to prevent life but as one
that would save life--the church might well have said yes. Hadn't Pius XII
already approved the Pill for therapeutic purposes? Rock would only have had to
think of the Pill as Pike thinks of it: as a drug whose contraceptive aspects
are merely a means of attracting users, of getting, as Pike put it, "people who
are young to take a lot of stuff they wouldn't otherwise take."

But Rock did not live long enough to understand how things might
have been. What he witnessed, instead, was the terrible time at the end of the
sixties when the Pill suddenly stood accused--wrongly--of causing blood clots,
strokes, and heart attacks. Between the mid-seventies and the early eighties,
the number of women in the United States using the Pill fell by half. Harvard
Medical School, meanwhile, took over Rock's Reproductive Clinic and pushed him
out. His Harvard pension paid him only seventy-five dollars a year. He had
almost no money in the bank and had to sell his house in Brookline. In 1971,
Rock left Boston and retreated to a farmhouse in the hills of New Hampshire. He
swam in the stream behind the house. He listened to John Philip Sousa marches.
In the evening, he would sit in the living room with a pitcher of martinis. In
1983, he gave his last public interview, and it was as if the memory of his
achievements was now so painful that he had blotted it out.

He was asked what the most gratifying time of his life was. "Right
now," the inventor of the Pill answered, incredibly. He was sitting by the fire
in a crisp white shirt and tie, reading "The Origin," Irving Stone's fictional
account of the life of Darwin. "It frequently occurs to me, gosh, what a lucky
guy I am. I have no responsibilities, and I have everything I want. I take a
dose of equanimity every twenty minutes. I will not be disturbed about
things."

Once, John Rock had gone to seven-o'clock Mass every morning and
kept a crucifix above his desk. His interviewer, the writer Sara Davidson, moved
her chair closer to his and asked him whether he still believed in an
afterlife.

"Of course I don't," Rock answered abruptly. Though he didn't
explain why, his reasons aren't hard to imagine. The church could not square the
requirements of its faith with the results of his science, and if the church
couldn't reconcile them how could Rock be expected to? John Rock always stuck to
his conscience, and in the end his conscience forced him away from the thing he
loved most. This was not John Rock's error. Nor was it his church's. It was the
fault of the haphazard nature of science, which all too often produces progress
in advance of understanding. If the order of events in the discovery of what was
natural had been reversed, his world, and our world, too, would have been a
different place.

"Heaven and Hell, Rome, all the Church stuff--that's for the
solace of the multitude," Rock said. He had only a year to live. "I was an
ardent practicing Catholic for a long time, and I really believed it all then,
you see."

Welcome neecee... I'm glad you found us too! hope all goes well with the onc....

Welcome neecee!  Lots of stage 2 sisters here,  all at different places in treatment and post treatment.  Let us know if you have any questions and any way we can help you.  I am sure your onc will have a plan for you this week so you can get started with your next stage of treatment. Just let us know how we can help and support you.

All, I feel like such a Debbie downer or whined this morning. Felt like this weekend no matter how much I read or go over my pathology report the BC is what it is. I can't wonder about why they did not find this a year earlier, etc. Believe me, I realize I am in a good place and that I am fortunate my BC is treatable. Maybe this is just the next step in moving on. I have finished rads, chemo, surgery and am just hang herceptin now. Maybe it is just that treatments are winding down and I feel a loss of control. Thanks for letting me vent. I am really not a whiner. Libraylil

lil - you are most certainly not a whiner! You've been through a lot and treatment has been a major part of your day for many months. When I was finished, I was like, "well, what's next?". I felt like I lost my safety net, but like my son constantly reminds me, "Your cancer is gone and you need to start thinking of it that way". I know he's right - I think it just takes time for that feeling of certainty to come but I think I'm getting better about putting this on the back burner. I guess I'm just starting to reach the "moving on" phase, too. And I'm sooooo happy about it!

sanbar - I've always been concerned about my WBC since chemo, so I try to eat foods that boost the immune system and I take supplements to help support it. I just think it's a good idea to do that for at least the first year after chemo because our immune system takes such a beating. Plus, I think those levels will fluctuate from month to month. About 2 months ago, my WBC was just on the low edge of the acceptable range, and I was worried about it and then the next month it was practically powerful!

This first year I'm seen every 6 months by my onc and every 6 months by my BS. I think after a year I might only have to see each of them yearly but that will be my onc's call. Not sure what happens after 5 years.

I did scans before my surgery to make sure I wasn't stage IV… if I was they would have done chemo first. There was something on my liver that they thought was probably cysts but to be sure they scanned again after chemo. Still looks like cyst but said they want to scan again in a year to be sure. (This rescan shit actually makes me nervous. Am I OK or what? I guess they are just being extra careful since HER2 likes to hang out in the liver).

I'm still doing treatment because I'm HER2+… herceptin every 3 weeks for a year. Also I'm on Anastrozole for 5 years. I assume they have you on Tamoxifen. That's still treatment. Tamoxifen should starve any of those cancer cells IF for some reason some are still hanging out and get turned on all of a sudden.

But think of it this way. You can get hit by a car if you cross the street. You still don't worry about crossing the street. You take the proper precautions and don't think about the worst. Same thing with breast cancer. You do what you need to do to keep your recurrence risk down and live your life. If something isn't right you go see the doctor… otherwise you will worry and waste your energy better spent on living.

heartnsoul76, I see we have the same staging and grade.  What can you tell me about what went into tyour decision to do chemo?  I am meeting with my onc for the first time this Friday, and am trying to be as prepared as I can.  Any insight/input would be most appreciated.

lago, good point.  I will ask the onc about it.

neecee - funny you should ask, because it was a toss-up until a specific incident happened. I was thinking about forgoing chemo (and I preferred not to do it, who really wants to if you think you have a choice?), My onc approved my participation in the TailorX trial where Early Stage BC patients either get hormones only or chemo and hormones (they are trying to determine whether chemo is beneficial for us or not). Well.....she WAS okay with it either way but then we were having a final meeting about my participation in this trial with my onc and the nurse from the trial. I was just asking questions from my notes, I didn't even really know what I was asking. But when I asked what grade my tumor was, the onc didn't know and the nurse and onc started fumbling through the papers and my onc said, "Oh, you're a Grade 3." Then she proceeded to explain that is the most aggressive type and then all of a sudden she blurted out, "My instincts tell me you need chemo." It surprised everyone because she was not supposed to favor one option over the other one for this trial. I asked why, and she said because of the size of your tumor (2.5 cm) and the fact that it was a Grade 3. And she said that even though I had no signs of lymph or vascular invasion, a tumor that has grown fairly large has a better chance of some rogue cancer cells breaking away. And of course, finding out it was an aggressive Grade 3 tumor also concerned me.

And I trusted HER instincts about this subject better than mine! She is the doctors' oncologist around here (Atlanta/Decatur) and all of my doctors that are completely unrelated to my cancer treatment comment on how 'she's who their wife went to see', or 'you're lucky if you can get in to see her' kind of thing. In fact, I ended up with a dream team. The RO and the MO are the best - people come from 60 miles away to see them (I've met some of them). And they bypass Emory Hospital (which has a great cancer center) to see these two. So, I trust their judgment completely. They've seen everything, so often, I wasn't going to argue. Also, one other thing - when I called the people from the TailorX trial and told them I decided not to participate and that I was going to do the chemo, the nurse in charge of the program here in Atlanta said, "Well, for what it's worth, I think you made the right decision."

The other part that left me undecided was my Oncotype and my KI67. Oncotype was 17, KI67 was 19. They are both basically intermediate, so that was no help. If one or the other was extreme, it would have been a deciding factor, but falling in the middle pretty much put the chemo decision back on my plate.

You know sometimes when you ask people point blank about something, you get kind of a "hedged" answer. I felt so lucky to get a kind of "caught off-guard" remark.

LOL - probably WAY more info than you needed, but I wanted you to know all the variables that came into play and how I felt about each one. Sheesh - it's like information overload, isn't it? I think by the time we're all about a year into this, our oncs think we're PITAs because we've researched the hell out of everything.

Good luck at your appointment on Friday, and I hope you get some good answers and you like your onc, too! 

Heart. For what it is worth I think you made the right decision. You will never regret having the chemo. Kick cancers sorry azz with all you ve got. Libraylil

Neecee,

To answer your question about whether to do chemo.  There are times in your life when you put your fate in the hands of experts.  I am not an expert in cancer treatment.  My oncologist is, and I knew going into this whole experience that I would die if I did not get help.

When I was told that I had a 50% chance of making it without chemo/hormonal therapy, and a better than 80% chance with, you didn't have to ask me twice whether I should do chemo.

This is a time when you need to make a "worst case" assumption.  That is, surgery didn't get all the stray cancer cells and that they are roaming around elsewhere in your body.  Chemo is a "search and destroy" deal, and hormonal therapy creats an unfavorable environment for anything that the chemo missed to grow.

I am grateful to be here.  I am strong and healthy at this point, and continuing on with my life.

These are years that I would not have had otherwise.

I am beyond grateful for them.  And grateful for a multitude of other blessings. - Claire

I had a stereotactic core biopsy on 5/2 that showed 2 areas of low grade DCIS.

I had 2 additional areas with a core needle biopsy on 5/9; left lower outer quadrant mass,and left periareolar mass.They both show IDC grade 2.

I'm having an MRI on 5/16,and have an appointment with an oncologist on 5/20. I also will be having chest x-ray,and lab work.

It will then be decided if I have surgery or chemo first.

The scariest part is that I've had mammograms every year since I was in my early 30's (now 64), and the 2 areas with the IDC did not show on the mammograms! Had a fibroadenoma removed in my early thirties,and have always had a lot of calcifications.

Now another 9 days of waiting.

cheryl - waiting is the hardest part! I hope everything turns out well. I dislike mammograms not only because they hurt like the dickens, but because they have such a low percentage of accurately detecting tumors. When it was time for my first mammogram after my lumpectomy, I went along with it reluctantly simply because that's what all of my doctors are used to reviewing for changes. I knew it would hurt, and it still hurts one month later. I go back again in 5 months, and I think I will ask for a breast MRI this time.

neecee - good luck with your onc appointment tomorrow! Let us know what he/she says - it's always nice to hear what someone else's onc says so we can compare notes.

claire - I love the way your mind works. Just bam, bam, DONE! I tend to over-think things, and I'm working on changing that trait. Actually, I think it's a learned trait from 20 years with my ex and his family - I need to undo some of their loony influences on me. I remember telling him after we had been married for just a few months, "If I had known you were the most normal member of your family, I would have never married you."