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There is a steady drumbeat of peer-reviewed medical articles relating risks of breast cancer from a variety of factors. Whether or not the reported factors are under the control of any given individual, they have been trumpeted by the lay media and are responsible for the understandable finding among women that breast cancer generates more anxiety than heart disease, even though the number of US women who died of heart disease in 2010 is over seven and a half times the number who fell victim to breast cancer. This article attempts to reduce the anxiety-inducing barrage of these reports by orienting physicians to better understand the validity of reported breast cancer risk factors. We hope to provide this understanding by: explaining the difference between relative and absolute risk, encouraging application of the 95% confidence interval to better evaluate the statistical validity of any given risk factor; placing the reported risk factors in the context of an accepted risk factor like cigarette smoking and lung cancer; and communicating the limits of statistical validity in the absence of reproducibility. This review will, to a small degree, provide a balance to the reports currently dominating the literature.
CLIMACTERIC 2011; Early Online, 1–6
OPINION Received 31-07-2011
© 2011 International Menopause Society Revised 03-09-2011
DOI: 10.3109/13697137.2011.624215 Accepted 13-09-2011
Correspondence: Dr A . Z. Bluming, Hematology Oncology Medical G roup of the San Fer nando Valley, 16133 Ventura Boulevard, Encino, 91436 USA
Association. Only 8% of women recognized that heart
disease and stroke were the leading cause of death, and
killed more women each year than the next 16 causes of death
combined including diabetes, all forms of cancer, AIDS,
and accidents
3 . Even among a population of 63 566 women
with diagnosed breast cancer who were 66 years of age or
older at diagnosis, heart disease was responsible for more
deaths than breast cancer
4 .
To date, the strongest known factors that signifi cantly
increase the risk of breast cancer are, unfortunately, out of an
individual woman s control: being female, increasing age
5,6 ,
having a strong family history of breast cancer, and carrying
one of the genes associated with an increased tendency to
develop breast cancer, of which the most important are cur-
rently acknowledged to be BRCA1 and BRCA2. This latter
congenital risk factor has been estimated to increase the life-
time risk of breast cancer by almost seven-fold
7,8 .
With this state of affairs, it is not surprising that identifying
controllable risk factors that may contribute to future breast
cancer development has become a minor industry. And so,
with dizzying frequency, yet another epidemiological study
makes headlines, yet another food or behavior is announced
that increases a woman s risk of breast cancer. These studies,
which are almost always further sensationalized and exagger-
ated by the media, both refl ect women s anxiety about breast
cancer and amplify it.
American women are understandably frightened of developing
breast cancer, the most common cancer affecting women in
this country. The American Cancer Society estimates that, in
2010, about 207 000 women developed invasive breast can-
cer; 54 010 developed non-invasive breast cancer; and 39 840
died of breast cancer
1 . And yet 90% of the women who are
diagnosed with breast cancer this year will probably be cured
following initial treatment
2 .
In spite of that heartening statistic, breast cancer generates
more anxiety than heart disease even though the number of
US women who died of heart disease in 2010 (306 246) is
over seven and a half times the number who fell victim to
breast cancer
1 . Some have suggested that the reason women
fear breast cancer more than heart disease is that breast cancer
affects women at a younger age than does heart disease.
However, in every decade over age 40, more women die of
heart disease than die of breast cancer
1 . This disproportionate
fear is not a new fi nding. Over 13 years ago, an editorial in
The Lancet noted: in a survey commissioned by the
National Council on the Aging (NCOA) of 1000 women
between the ages of 45 and 64, 61% said that the disease they
most feared was cancer predominantly breast cancer. By
contrast, only 9% said that the condition they most feared
was the disease most likely to kill them heart disease. The
editorial added: These fi ndings are almost identical to a sur-
vey released earlier this year (1997) by the American Heart
What are the real risks for breast cancer?
A. Z. Bluming and C. Tavris *
Hematology Oncology Medical Group of the San Fernando Valley, Encino; * Social Psychologist, Los Angeles, USA
There is a steady drumbeat of peer-reviewed medical articles relating risks of breast cancer from a variety of
factors. Whether or not the reported factors are under the control of any given individual, they have been
trumpeted by the lay media and are responsible for the understandable fi nding among women that breast
cancer generates more anxiety than heart disease, even though the number of US women who died of heart
disease in 2010 is over seven and a half times the number who fell victim to breast cancer. This article attempts
to reduce the anxiety-inducing barrage of these reports by orienting physicians to better understand the valid-
ity of reported breast cancer risk factors. We hope to provide this understanding by: explaining the difference
between relative and absolute risk, encouraging application of the 95% confi dence interval to better evaluate
the statistical validity of any given risk factor; placing the reported risk factors in the context of an accepted
risk factor like cigarette smoking and lung cancer; and communicating the limits of statistical validity in the
absence of reproducibility. This review will, to a small degree, provide a balance to the reports currently
dominating the literature.
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What are the real risks for breast cancer? Bluming and Tavris
2 Climacteric
Although there is no shortage of published risk factors,
there is a shortage of critical assessments of what they mean.
Table 1 lists many of the published risk factors linked to breast
cancer incidence. A risk factor of less than 1 suggests a reduced
risk; a risk of 1 suggests the factor confers neither an increased
nor a decreased risk of breast cancer. A risk factor of greater
than 1 suggests an increased risk. A risk of 1.14 means a 14%
increased risk.
The risks listed in this table are expressed as relative risks,
the way they are typically reported by researchers and then
by the media. The problem is that relative risks often appear
to be more important than they are
9 . Two major consensus
projects on the reporting of clinical trials have concluded
that stating relative risks alone is often deceptive; results
should be provided in absolute numbers, not only as percent-
age changes
10–13 . For example, if we read that the relative
Table 1 Risk factors reported to be associated with the development of breast cancer
Relative risk 95% confi dence interval Reference
Dietary fi ber intake 0.31 0.20 0.47 27
Signifi cant weight gain from age 21 to present 0.52 0.32 0.83 28, 29
Garlic and onions 7 10 ti mes/week 0.52 0.340.78 30
High level of stress 0.60 0.37 0.97 31
Grapefruit 0.60 0.37 0.98 32
Fish oil 0.68 0.50 0.92 33
Large body build at menarche 0.69 0.49 0.96 28, 29
Conjugated equine estrogen 0.77 0.59 1.01 34
Aspirin 0.80 0.71 0.90 35
Coffee consumption 5 cups/day 0.80 0.64 0.99 36
Above average weight at 12 years 0.85 0.74 0.98 37
Low income 0.85 0.84 0.87 38
Cigarette smoking 1.06 1.01 1.10 39
Birth weight 1.09 2.00 17.0 0 40
Fish intake 1.14 1.03 1.26 41
Birth length 51 c m 1.17 1.02 1. 35 42
Use of antihypertensive medicine 5 years 1.18 1.02 1. 36 43
Exposure to light at night 1.22 1.121.31 44
Cigarette smoking 1.24 1.06 1.44 45
Premarin/progestin 1.24 1.01 1.54 46
Premarin/progestin 1.26 1.00 1.59 47
Alcohol 1.26 1.06 1.44 45
French fries (1 additional serving /week) 1.27 1.12 1.4 4 48
Physical abuse in adulthood 1.28 1.07 1.52 49
Grapefruit 1.3 1.06 1.58 50
Digoxin (current users) 1.39 1.32 1.46 51
Night shift work 1.51 1.36 1.68 52, 53
15 kg weight gain during pregnancy 1.61 1.03 2.52 54
Cigarettes at least 10/day 1.7 1.20 2.43 55
Flight attendant (Finnish) 1.87 1.15 2.23 56, 57
40 years old (premenopausal breast cancer) 1.9 1.12 3.26 58
Dutch famine 2.01 0.92 4.41 59
Placental weight 2.05 1.15 3.64 60
Antibiotic use 2.07 1.48 2.89 61
Increased carbohydrate intake 2.22 1.63 3.04 62
Left-handedness (premenopausal) 2.41 1.35 4.30 63
Intercristal width * of 30 cm in a mother who was born 40 weeks gestation 3.7 2.1 6.8 64
Flight attendant (Icelandic) 4.1 1.70 8.50 65
Betel quid chewing 4.78 2.87 8.00 66
Electric blanket use 4.9 1.5015.6 67
Vitamin D defi ciency 5.83 2.31 14 .7 68, 69
Intercristal width * of 30 cm in a mother who had given bir th previously 7.2 3.4 15.4 64
Tobacco smoking and lung cancer 26.07 6.58 103.3 70
* , The intercristal width is the maximal width bet ween the iliac crests
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What are the real risks for breast cancer? Bluming and Tavris
Climacteric 3
risk of breast cancer is increased by 300% in women who
eat a bagel every morning, that sounds serious, but it is not
informative. We would need to know the baseline absolute
number of new breast cancer patients before introduction of
the risk factor. If the number shifted from one in 10 000
women to three in 10 000 women, that is a 300% relative
increase, but, as an absolute increase of only 2 per 10 000,
it is very likely a random artifact. If the risk had jumped
from 100 to 300 per 10 000, also a 300% relative increase,
we might reasonably be concerned. In large epidemiological
studies that generally include tens of thousands of people, it
is very easy to fi nd a small relationship that may be considered
signifi cant by statistical convention but which, in practical
terms, means little or nothing because of the low absolute
A reliance on relative risks alone can mistakenly infl ate the
results of medical studies. In 1998, tamoxifen was reported
to show a 48% decrease in breast cancer development com-
pared to placebo when administered to healthy women
believed to be at increased risk of the disease (i.e. they were
female, and they were over 60)
14 . Yet the absolute difference
between the treatment group and the control group was only
1.3% (2.7% vs. 1.4%)
15 . Should healthy women really be
given tamoxifen on the basis of such a trivial difference? The
study, however, was widely publicized as having found a
nearly 50% decrease in risk .
This is why scientists who are working to promote statisti-
cal literacy, especially in helping the public and physicians
understand actual versus infl ated risks of diseases and treat-
ments, emphasize that knowing the baseline of absolute num-
bers when comparing two groups is essential
9 . It is also why
they are encouraging scientists to move away from the tradi-
tional reliance on statistical signifi cance and replace it with
measures of a relationship’ s strength
16–22 . One such measure
is the confi dence interval (CI)
23,24 . A 95% CI provides a range
(an interval) with a specifi ed probability that a given result,
with continued replications, will be due to chance only 5%
of the time. In the case of large-scale epidemiological studies,
if the spread of the confi dence interval includes the
number 1.0, the result is usually considered not statistically
signifi cant. Generally speaking, the lower limit of the 95% CI
should be at least 3.0 before the fi nding is considered a strong,
reliable one
25 .
Now take another look at Table 1. To put matters in
perspective, we included one factor that has reliably, with
extensive replications, been linked to cancer: cigarette smok-
ing and lung cancer. None of the other factors listed here have
been consistently shown to be important as a risk factor for
breast cancer development. On the contrary, most are the
result of post-hoc statistical manipulation, such as data
mining or retrospective substratifi cation, in an effort to fi nd
a publishable, signifi cant result
26 .
For example, the association with exposure to the Dutch
59 was found only among women who were exposed
to severe famine when they were between the ages of 2 and
9. The association with antibiotics
61 depended upon the
indication for antibiotic administration. The association with
electric blanket use
67 was most pronounced for those using
the device for more than 10 years, but only after the women
who used it for more than 6 months per year were omitted.
A decreased risk reported in association with grapefruit
32 related only to estrogen receptor-negative (ER-) pro-
gestogen receptor-negative (PR-) tumors and was found only
among women eating one or more grapefruit per day, while
eating only a quarter of a grapefruit per day was associated
with an increased breast cancer risk
50 . The increased risk
among women on antihypertensive medication
43 was confi ned
to those with ER tumors and held only for pre- or perimeno-
pausal women. The increased risk associated with digoxin
was noted only among current users. Some of the associations
appear absurd, such as that linking an increased risk of breast
cancer to one additional serving of French fries per week dur-
ing childhood
48 . And how can eating a quarter of a grapefruit
every day increase a woman s risk
50 while eating one or more
grapefruit reduces it
32 ?
Of the 40 separate risk factors listed in Table 1, two
alcohol use and hormone replacement therapy have gar-
nered the most attention, reporting an increased relative risk
of 24 26%. So let us consider these factors more closely. The
ndings on alcohol are a mess of inconsistencies and data
mining: alcohol has most recently been reported to increase
breast cancer risk only in women who imbibed at least 15 g
per day or approximately seven drinks per week, but this
association was noted only among those women with ER
breast cancer
45 . The increased risk was reported in three
case control studies
71–73 and two cohort studies
74,75 , but four
other case control studies
76–79 and another cohort study
failed to confi rm this result. Other research suggests that there
are good health-related reasons to limit alcohol ingestion, but
fear of breast cancer should not be one of them.
The most widely publicized risk factor in Table 1 is that
reportedly associated with postmenopausal HRT
46,47 , inges-
tion of conjugated equine estrogen alone or in conjunction
with progestin. Notice, however, that the increased relative
risk was minor (24% and 26%) and weak (the confi dence
interval contains a 1 for the 26% increased risk). The clini-
cal signifi cance of this association and the benefi t/risk ratio
of HRT remain subjects of active debate, given that the
ndings have been contradicted by many other studies
81 .
Indeed, although estrogen was the original candidate for the
suggested association between HRT and breast cancer, and
hence the marketing of the original selective serotonin
receptor modu lators (SERMs) as estrogen blocking agents,
recently estrogen alone has been reported to decrease breast
cancer risk
34,82 .
In order to make intelligent health decisions for ourselves
and those under our care, we must be able to balance the
potential benefi ts of a medication, a food, a vitamin, or an
activity against potential risks. We can do this only when the
data are presented to us clearly and accurately
83,84 , without
an attempt to dazzle us with alleged alarms and break-
throughs that use statistics to disguise actual results.
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What are the real risks for breast cancer? Bluming and Tavris
4 Climacteric
One may legitimately wonder about the motivations
behind the publication of so much misleading information
85 .
Although he used the word passions, not statistics, Roger
L Estrange s warning, written over three centuries ago, reso-
nates today. He said: It is with our passions as it is with
re and water, they are good servants but bad masters
86 .
Confl ict of interest A.Z.B. has, in the past, been
compensated on an hourly basis for testimony as an expert
witness on behalf of defendant, Wyeth Pharmaceuticals.
Source of funding Nil.
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... The incidence of breast cancer in Hispanic women is 26% lower than non-Hispanic White women. This is most likely due to differences in reproductive choices such as age of first pregnancy, number of pregnancies and rate of hormone supplementation use [10]. However, in Hispanic women breast cancer is often detected when it has reached a more advanced stage compared to non-Hispanic White women (64% in non-Hispanic Whites detected at local stage versus 56% in Hispanics) [4]. ...
... Cancer can occur as a result of various factors, including inherited and acquired genetic mutations, diet, lifestyle choices and age [10,12]. It has long been recognized that cancer risk is higher in some families and ethnic groups as compared to the population at large, suggesting a genetic component to the overall breast cancer risk. ...
... The endogenous risk of breast cancer is 2.8% by age 60 years, while the putative risk of breast cancer increases to 3.37% with HT use for 5 years; the absolute increase is 0.67% (Santen et al., 2012). This is inferior to the risk of developing breast cancer conferred by obesity, by being a flight attendant, or by other common exposures (Bluming and Tavri, 2012). Finally, appropriate follow-up during HT usually allows diagnosing tumors with no discernible difficulty compared to nonusers (Cheek et al., 2002). ...
Full-text available
BACKGROUND Menopausal symptoms can be very distressing and considerably affect a woman’s personal and social life. It is becoming more and more evident that leaving bothersome symptoms untreated in midlife may lead to altered quality of life, reduced work productivity and, possibly, overall impaired health. Hormone therapy (HT) for the relief of menopausal symptoms has been the object of much controversy over the past two decades. At the beginning of the century, a shadow was cast on the use of HT owing to the concern for cardiovascular and cerebrovascular risks, and breast cancer, arising following publication of a large randomized placebo-controlled trial. Findings of a subanalysis of the trial data and extended follow-up studies, along with other more modern clinical trials and observational studies, have provided new evidence on the effects of HT. OBJECTIVE AND RATIONALE The goal of the following paper is to appraise the most significant clinical literature on the effects of hormones in postmenopausal women, and to report the benefits and risks of HT for the relief of menopausal symptoms. SEARCH METHODS A Pubmed search of clinical trials was performed using the following terms: estrogens, progestogens, bazedoxifene, tibolone, selective estrogen receptor modulators, tissue-selective estrogen complex, androgens, and menopause. OUTCOMES HT is an effective treatment for bothersome menopausal vasomotor symptoms, genitourinary syndrome, and prevention of osteoporotic fractures. Women should be made aware that there is a small increased risk of stroke that tends to persist over the years as well as breast cancer risk with long-term estrogen–progestin use. However, healthy women who begin HT soon after menopause will probably earn more benefit than harm from the treatment. HT can improve bothersome symptoms, all the while conferring offset benefits such as cardiovascular risk reduction, an increase in bone mineral density and a reduction in bone fracture risk. Moreover, a decrease in colorectal cancer risk is obtainable in women treated with estrogen–progestin therapy, and an overall but nonsignificant reduction in mortality has been observed in women treated with conjugated equine estrogens alone or combined with estrogen–progestin therapy. Where possible, transdermal routes of HT administration should be preferred as they have the least impact on coagulation. With combined treatment, natural progesterone should be favored as it is devoid of the antiapoptotic properties of other progestogens on breast cells. When beginning HT, low doses should be used and increased gradually until effective control of symptoms is achieved. Unless contraindications develop, patients may choose to continue HT as long as the benefits outweigh the risks. Regular reassessment of the woman’s health status is mandatory. Women with premature menopause who begin HT before 50 years of age seem to have the most significant advantage in terms of longevity. WIDER IMPLICATIONS In women with bothersome menopausal symptoms, HT should be considered one of the mainstays of treatment. Clinical practitioners should tailor HT based on patient history, physical characteristics, and current health status so that benefits outweigh the risks.
... Breast cancer is the most frequent malignant disease and the leading cause of death due to cancer among women in the world, and In Iraq, it is the commonest type of female malignancy, accounting for approximately one-third of the registered female cancers [1]. The disease is associated with several risk factors, and epidemiological studies have suggested that menopause, oral contraceptive use, body mass index (BMI) and family history of breast cancer or other cancers may have different relations to the disease [2]. Other risk factors may include some immunogenetic markers; for instance ABO blood groups [3]. ...
Full-text available
The study involved 120 women, who were distributed into two groups of breast tumor patients (30 malignant and 30 benign) and a group of controls (60 women). The patients were referred to the Center for Early Detection of Breast Tumor at Al-Alwayia Hospital for Gynecology and Obstetrics (Baghdad) during the period June-December 2011. They were investigated for the frequency of ABO blood group phenotypes, menopausal status, oral contraceptive use, body mass index and family history of breast cancer or other cancers. The results demonstrated that 60.0% of malignant cases clustered after the age 50 years, while it was 20.0% in benign cases. Fifty percent of malignant breast tumor patients reached menopause, while in benign cases, the corresponding frequency was much lower (20.0%). It was also observed that 60.0% of malignant patients used oral contraceptives, while such frequency was lower in benign patients (20.0%). Overweight and obese cases were observed with a frequency of 43.3 and 26.7%, respectively in malignant patients, and the corresponding frequencies in benign patients were 36.7 and 33.3%, respectively. Positive family history of malignant breast cancer accounted for 43.3% in malignant cases, while in benign cases; it was less frequent (20.0%). The distribution of ABO blood group phenotypes demonstrated a significant difference (P ≤ 0.05) between malignant patients and controls, but not between benign patients and controls. Such significant difference was mainly contributed by an increased frequency of B phenotype (36.7 vs. 16.7%) and a decreased frequency of O phenotype (26.7 vs. 55.0%) in malignant patients. 1 1 ‫يه‬ ‫المستنصر‬ ‫الجامعة‬ ‫العلوم،‬ ‫كلية‬ ‫الحياة،‬ ‫علوم‬ ‫قسم‬. 2 ‫بغداد‬ ‫جامعة‬ ‫العلوم،‬ ‫كلية‬ ‫ة،‬ ‫الحار‬ ‫للمناطق‬ ‫البيولوجية‬ ‫البحوث‬ ‫وحدة‬. ‫الخالصة‬ : ‫اسة‬ ‫الدر‬ ‫شملت‬ 021 ‫أة‬ ‫امر‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫من‬ ‫مجموعتين‬ ‫على‬ ‫توزعت‬ (01 ‫و‬ ‫خبيث‬ 01 ‫حميد‬) ‫ومجموعة‬ ‫ة‬ ‫سيطر‬ (01 ‫أة‬ ‫امر‬ .) ‫للنسائية‬ ‫العلوية‬ ‫مستشفى‬ ‫في‬ ‫الثدي‬ ‫ام‬ ‫ألور‬ ‫المبكر‬ ‫الكشف‬ ‫لمركز‬ ‫اجعات‬ ‫مر‬ ‫يضات‬ ‫المر‬ ‫كانت‬ ‫ان‬ ‫ير‬ ‫حز‬ ‫ة‬ ‫وللفتر‬ ‫بغداد‬ ‫في‬ ‫التوليد‬ ‫و‬-‫األول‬ ‫كانون‬ 2100. ‫درست‬ ‫اليأسية‬ ‫الحالة‬ ‫و‬ ‫الدم‬ ‫مجاميع‬ ‫يع‬ ‫لتوز‬ ‫يضات‬ ‫المر‬ ‫الحمل‬ ‫انع‬ ‫مو‬ ‫استعمال‬ ‫و‬ ‫الفموي‬ ‫ة‬ ‫أخرى‬ ‫سرطانات‬ ‫أو‬ ‫الثدي‬ ‫لسرطان‬ ‫العائلي‬ ‫يخ‬ ‫التار‬ ‫و‬ ‫الجسم‬ ‫كتلة‬ ‫ودليل‬. ‫أوضحت‬ Abdul-Jabbar 1037 ‫بأن‬ ‫النتائج‬ 01 % ‫العمر‬ ‫بعد‬ ‫كانت‬ ‫الخبيث‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫من‬ 01 ‫في‬ ‫النسبة‬ ‫كانت‬ ‫حين‬ ‫في‬ ‫سنة،‬ ‫ه‬ ‫الحميد‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫ي‬ 21 .% ‫اليأس‬ ‫لسن‬ ‫وصلت‬ ‫التي‬ ‫و‬ ‫الخبيث‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫نسبة‬ ‫وكانت‬ ‫هي‬ 01 % ‫الحميد‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫في‬ ‫أقل‬ ‫النسبة‬ ‫هذه‬ ‫كانت‬ ‫حين‬ ‫في‬ ، (21 .)% ‫وفضال‬ ‫فأن‬ ‫ذلك‬ ‫عن‬ 01 % ‫الخبيث‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫من‬ ‫استخدمت‬ ‫الحمل‬ ‫انع‬ ‫مو‬ ‫الفموي‬ ‫ة‬ ‫يضات‬ ‫مر‬ ‫في‬ ‫أقل‬ ‫النسبة‬ ‫هذه‬ ‫وكانت‬ ، ‫الحميد‬ ‫الثدي‬ ‫ورم‬ (21 .)% ‫هي‬ ‫البدينات‬ ‫و‬ ‫الوزن‬ ‫في‬ ‫يادة‬ ‫ز‬ ‫تمتلك‬ ‫التي‬ ‫الخبيث‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫نسبة‬ ‫وكانت‬ 30.0 ‫و‬ 20.2 % ‫هي‬ ‫الحميد‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫في‬ ‫ة‬ ‫المناظر‬ ‫النسب‬ ‫كانت‬ ‫حين‬ ‫في‬ ‫الي،‬ ‫التو‬ ‫على‬ ، 00.2 ‫و‬ 00.0 % ‫الي‬ ‫التو‬ ‫على‬ ،. ‫أظهرت‬ ‫و‬ 30.0 % ‫لسرطان‬ ‫موجب‬ ‫عائلي‬ ‫يخ‬ ‫تار‬ ‫الخبيث‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫من‬ ‫ا‬ ‫الحميد‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫في‬ ‫أقل‬ ‫النسبة‬ ‫هذه‬ ‫كانت‬ ‫حين‬ ‫في‬ ‫لثدي،‬ (21 .)% ‫وجود‬ ‫النتائج‬ ‫أوضحت‬ ‫كما‬ ‫فروقا‬ ‫مثل‬ ‫يظهر‬ ‫لم‬ ‫ولكن‬ ‫ة،‬ ‫السيطر‬ ‫ونساء‬ ‫الخبيث‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫مابين‬ ‫الدم‬ ‫مجاميع‬ ‫يع‬ ‫توز‬ ‫في‬ ‫معنوية‬ ‫ة‬ ‫السيطر‬ ‫ونساء‬ ‫الحميد‬ ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫مابين‬ ‫الفرق‬ ‫هذا‬. ‫الفرو‬ ‫هذه‬ ‫وتعود‬ ‫مجموعة‬ ‫ار‬ ‫تكر‬ ‫يادة‬ ‫لز‬ ‫المعنوية‬ ‫ق‬ ‫الدم‬ B (00.2 ‫مقابل‬ 00.2)% ‫الدم‬ ‫مجموعة‬ ‫ار‬ ‫تكر‬ ‫وقلة‬ O (20.2 ‫مقابل‬ 00.1)% ‫الثدي‬ ‫ورم‬ ‫يضات‬ ‫مر‬ ‫في‬ ‫الخبيث‬ .
... Il est important de replacer les risques dans leur contexte. Bien que la plupart des femmes estiment que le risque de cancer du sein constitue leur plus important risque m edical a vie, un grand nombre de donn ees indiquent que cette perception est fauss ee et que les femmes courent un risque a vie beaucoup plus important de mourir de MCV [68][69][70][71] . La probabilit e d'en venir a connaître un cancer du sein et d'en mourir pour chaque d ecennie est mise en contraste avec la probabilit e de mourir de diverses autres causes dans le Tableau 3.2 68 . ...
... In an observational study of hysterectomized women using conjugated equine estrogen 0.625 mg, breast cancer risk did not increase for at least 15 years, and this was predominantly seen in lean women (59). Increased body mass index is a significant endogenous risk factor for breast cancer, which is similar to, or exceeds the risk of HT (60,61). ...
The media attention surrounding the publication of the initial results of WHI in 2002 led to fear and confusion regarding the use of hormonal therapy (HT) after menopause. This led to a dramatic reduction in prescriptions for HT in the United States and around the world. Although in 2002 it was stated that the results pertained to all women receiving HT, subsequent studies from the Women's Health Initiative (WHI) and others clearly showed that younger women and those close to menopause had a very beneficial risk-to-benefit ratio. Indeed, the results showed similar protective effects for coronary disease and a reduction in mortality that had been shown in earlier observational studies, which had also focused on younger symptomatic women.In younger women, the increased number of cases of venous thrombosis and ischemic stroke was low, rendering them "rare" events using World Health Organization nomenclature. Breast cancer rates were also low and were found to be decreased with estrogen alone. In women receiving estrogen and progestogen for the first time in the WHI, breast cancer rates did not increase significantly for 7 years. Other data suggest that other regimens and the use of other progestogens may also be safer. It has been argued that in the 10 years since WHI, many women have been denied HT, including those with severe symptoms, and that this has significantly disadvantaged a generation of women. Some reports have also suggested an increased rate of osteoporotic fractures since the WHI. Therefore, the question is posed as to whether we have now come full circle in our understanding of the use of HT in younger women. Although it is appropriate to treat women with symptoms at the onset of menopause, because there is no proven therapy for primary prevention, in some women the use of HT for this role may at least be entertained.
Menopausal hormone therapy (MHT) has been used for prevention and treatment of postmenopausal osteoporosis for several decades. However, public concerns were raised over the safety of MHT after the initial report was published in 2002 by the Women’s Health Initiative. We conducted a historical review on this subject, primarily focusing on level I evidence from randomized controlled trials, systematic reviews and meta-analyses, and summarized high-quality evidence on the efficacy and safety of MHT in management of postmenopausal osteoporosis. Clinical issues were also discussed on MHT initiation, identification of treatment candidates and treatment duration, as well as discontinuation of MHT.
Many factors are considered when a woman estimates her personal risk of breast cancer. Common to most decisions are four separate influences that have convinced the public and many health-care providers that breast cancer is the greatest concern for menopausal women and that menopausal hormone therapy (MHT) is generally responsible. Historically there have been well-documented situations in which big pharma and doctors have not put patient interests first. Conflicting reports about the safety of MHT and the media imperative to always increase readership by presenting a compelling scary story have created an underlying distrust of science, doctors, and MHT. Numerical and statistical illiteracy in the general population creates a situation where lotteries succeed despite astronomical odds and the risks of medical interventions are exaggerated by their description using relative, rather than absolute, risks. Finally, mammographic overdiagnosis contributing to improved breast cancer survival has contributed to the ‘popularity paradox’ (more screening – more enthusiasm) especially among survivors and advocacy groups. As a result, worry about breast cancer has overshadowed concern about cardiovascular diseases as the major cause of death and disability in the later years. The ongoing challenge for clinicians dealing with menopausal women is to bridge the gap in risk perception with evidence-based common-sense advice.
With the increase in life expectancy, a woman may now expect to spend one-third or more of her life after menopause. Thus the understanding of the physiology of menopause and aging and possible management strategies assumes great significance for women's health. This review will first discuss the epidemiology of menopause, early or premature menopause, and the effects of menopause on various organ systems and diseases that occur after menopause. This will be followed by a consideration of various therapies for the symptoms of menopause, osteoporosis, and various preventative strategies for women after menopause. Hormonal and nonhormonal therapies will be discussed.
For several decades, the role of hormone-replacement therapy (HRT) has been debated. Early observational data on HRT showed many benefits, including a reduction in coronary heart disease (CHD) and mortality. More recently, randomized trials, including the Women's Health Initiative (WHI), studying mostly women many years after the the onset of menopause, showed no such benefit and, indeed, an increased risk of CHD and breast cancer, which led to an abrupt decrease in the use of HRT. Subsequent reanalyzes of data from the WHI with age stratification, newer randomized and observational data and several meta-analyses now consistently show reductions in CHD and mortality when HRT is initiated soon after menopause. HRT also significantly decreases the incidence of various symptoms of menopause and the risk of osteoporotic fractures, and improves quality of life. In younger healthy women (aged 50-60 years), the risk-benefit balance is positive for using HRT, with risks considered rare. As no validated primary prevention strategies are available for younger women (<60 years of age), other than lifestyle management, some consideration might be given to HRT as a prevention strategy as treatment can reduce CHD and all-cause mortality. Although HRT should be primarily oestrogen-based, no particular HRT regimen can be advocated.
Full-text available
Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS: Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS: This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood
The large-scale Women's Health Initiative has confirmed that, in postmenopausal women, combined estrogen/ progestin therapy entails an increased risk of invasive breast cancer. The investigators have now explored this relationship in detail, characterizing the cancers that developed and seeking to learn whether hormonal effects on the mammogram can influence diagnosis. A total of 16,608 postmenopausal women 50 to 79 years of age, all with an intact uterus, were randomly assigned to receive active treatment (0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate daily in a single tablet) or placebo. The participants, seen at 40 clinical centers, were to be followed from 1993 to 1998 by annual clinical breast examinations and mammograms, but the trial was ended after a mean interval of 5.2 years. Intent-to-treat analyses demonstrated a hazard ratio of 1.24 for both total cancers and invasive cancers in women given hormone therapy compared with the placebo group. There was some suggestion of an increased risk for in situ breast cancer in hormone-treated women. An increased risk of breast cancer in treated women emerged after 3 years in those not receiving hormones previously and after 2 years in previously treated women. The findings were similar when women in specific risk categories were analyzed, and race and ethnicity were not significant factors. Invasive cancers associated with combined hormone therapy were larger than those in placebo recipients, more likely to be node-positive, and diagnosed when more advanced. There was, however, no difference in tumor grade or in the distribution of histologic types of breast cancer. After the first year, hormone-treated women more often had abnormal or highly suspicious mammograms than did those given placebo. In this prospective, randomized trial, combined estrogen/progestin treatment of postmenopausal women increased both breast cancer risk and the frequency of abnormal mammograms requiring medical assessment. In addition, cancers in treated women were more advanced when diagnosed than was the case for placebo recipients.
This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility, along with the supporting scientific evidence. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis available through the USPSTF Web site ( The recommendation is also posted on the Web site of the National Guideline Clearinghouse (
This checklist can be used to improve the scientific quality and clinical usefulness of the published reports of clinical trials. Improved reports will provide more consistently complete and reliable information for use in clinical treatment decisions, meta-analyses, and the interpretation of findings across clinical trials.
To comprehend the results of a randomized, controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Discussion. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, for each intervention group, that are included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.