Download Breast Cancer

ORAL CONTRACEPTION IN A PATIENT WITH A FIRST DEGREE RELATIVE
WITH BREAST CANCER
P. Spinola
CEPARH, Salvador, Bahia, Brazil
Breast Cancer
The breast is a challenge to the gynecologist in the continuous struggle to secure early
cancer detection. Unfortunately, many gynecologists do not examine the breasts as part of a
routine physical examination. This group of sub-specialists may consider themselves
“pelvicologists” instead of recognizing that the Greek root gyne refers to the whole woman,
according to Robert L. Shirley, M.D..1 The gynecologist/obstetrician plays a crucial role in
the early detection of breast cancer in the asymptomatic patient. Breast examination by a
physician, mammography and breast self-examination are all methods of early detection
that can detect breast cancer at the localized and most treatable stage.
Cancer is a disease that will touch most of us directly or indirectly. One in three Americans
gets cancer at some time in his or her life, and one in five dies of it.2 Breast cancer is a
widespread, devastating and often fatal disease. Its incidence varies from one continent to
another, affecting one woman in eight in the United States, one in 12 in Europe but only
one in 80 in Japan.3 In Brazil, breast cancer is the leading cause of death from cancer in
women. The most recent data suggest that 28,340 new cases were diagnosed and 8,245
deaths occurred in the year 2000.4 The incidence of breast cancer in Brazil is 33.58 cases
per 100,000 women per year and the mortality rate from breast cancer is 9.78 deaths per
100,000 women per year. Cancer has been appropriately called a disease of genes. It is now
clear that most, if not all, cancers arise from a single cell whose genetic make-up has been
damaged in a manner that results in uncontrolled growth. Inherited mutations in the
BRCA1 and BRCA2 genes predispose women to both breast and ovarian cancer, often at a
young age.5 Breast cancer accounts for approximately one-third of all cancers in women
and is second only to lung cancer as the leading cause of cancer deaths in women.6
Perhaps no other disease or its treatment has evoked such strong feelings as has breast
cancer. The reasons for this are to be found both in our culture in general and in medicine
in particular. The breast, in certain contexts, is the symbol of motherhood, nourishment and
security, while in others it represents beauty and femininity. The breast thus constitutes an
integral part of the body image for the woman as well as for the man.
Carcinoma of the breast is one type of cancer for which a considerable amount of
information about its etiology has been accumulated. Although its ultimate cause is not
known, a number of factors which influence its occurrence have been identified.
Many epidemiologic features of breast cancer suggest that endogenous hormones are
important in the genesis of this disease. Risk is approximately 100 times higher in women
than men. In women, risk increases markedly with age from a few years after menarche to
menopause, and then increases less strongly with age after cessation of normal ovarian
function. The earlier in life that a woman begins menstruating, the greater her risk; and her
risk is also directly related to her age at menopause. Risk is reduced if the ovaries are
removed before menopause, and the younger the age at oophorectomy, the greater the
protection. Risk is directly related to the age at which a woman has her first full-term
pregnancy, and nulliparous women have about the same risk as women who delay their first
pregnancy until their mid-30s.7
Women with first or second degree maternal or paternal relatives with breast cancer are at
increased risk. Women of western industrialized countries are at greater risk than those in
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developing countries, and migrants moving from low to high risk countries, or their
descendants, eventually develop breast cancer at rates similar to those in their country of
adoption. Nutritional factors, especially dietary fats, have been implicated as a possible
explanation for the international variation in risk. Obese women may be at increased risk,
especially in their postmenopausal years. Risk is increased in women with benign breast
lesions characterized by proliferation of the ductal epithelium. Women who have been
exposed to ionizing radiation for a variety of reasons are also at increased risk of breast
cancer.7
Endocrinological studies based on total levels of various endogenous hormones in serum
and urine provided some clues to the factors than enhance risk of breast cancer.
The relationship between hormones and breast cancer has been discussed and debated for
nearly a century. Nevertheless, the history of this relationship has perplexed practitioners
because hormones were considered as carcinogenic or at least co-carcinogenic, while, on
the contrary, sometimes they were thought to protect against breast cancer. A summary of
the accusations and/or statements have often been based on debatable pathogenic
interpretations or on fragile hypothesis that was to rapidly transform into postulates. 8
In 1896, Beatson 9 suggested oophorectomy as a treatment of breast cancer. He was indeed
the first to publish that oophorectomy led to regression of metastatic breast cancer in some
patients.
A series of studies has much contributed to an understanding of the regulation of tumor
growth by hormones.
Oral Contraceptives (OCs) and Breast Cancer
Currently, more than 100 million women use OCs. OCs rank third among all family
planning methods currently used by married women, an estimated 8% compared to 19%
who rely on female sterilization and 13% using intrauterine devices (IUDs). In developed
countries, OCs are the most widely used method. OCs have substantial benefits for
women’s health. 10 The most important benefit, of course, is highly effective protection
against pregnancy. Other benefits include the convenience of OCs, the fact that they are not
intercourse-related and their reversibility. The OC offers the following classic noncontraceptive benefits to women’s health:
1. Lower rates of ovarian cancer
2. Lower rates of endometrial cancer
3. Fewer cases of benign breast disease
4. Fewer ovarian cysts
5. Fewer ectopic pregnancies
6. Less pelvic inflammatory disease (PID)
7. Less iron deficiency anemia
8. Less premenstrual syndrome (PMS)
9. Less dysmenorrhea and menorrhagia
10. Less osteoporosis
11. Less endometriosis
12. Fewer uterine fibroids
13. Less rheumatoid arthritis
14. Less acne
15. Probably less thyroid disease
16. Possibly fewer duodenal ulcers
17. Possibly less toxic shock syndrome (TSS)
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18. Obvious beneficial social effects
OCs reduce the incidence of endometrial and ovarian cancer. No such protective effect has
been observed against breast cancer. Numerous studies have shown that when statistics for
all ages are combined, breast cancer occurs with equal frequency in women who have and
have not used OCs. Women with a family history of breast cancer who have used OCs have
shown no significant change in the risk of breast cancer compared with women with a
family history who have not used OCs. It is probable that the women observed in any study
of the relationship between OCs and breast cancer were taking high-dose OCs, which are
no longer in use. In 199611, the Collaborative Group on Hormonal Factors in Breast Cancer
published an analysis that pooled epidemiological evidence from 54 studies in 25 countries,
covering over 53,000 women with breast cancer and over 100,000 without breast cancer.
These 54 studies constituted about 90% of the epidemiologic evidence available at the time.
The analysis examined a great many characteristics of OC use and users. Findings from the
pooled analysis include:
 Overall, women currently taking OCs or who have quit use within the past 10 years
were slightly more likely than nonusers to be diagnosed with breast cancer.
 Risk was greatest for current users and decreased with time between last use and
diagnosis. Relative risk was 1.24 for current users, 1.16 for women who had stopped
use within one to four years before diagnosis, and 1.07 for women who had stopped use
five to nine years before diagnosis.
 There was no additional risk for OC users who discontinued use 10 to 20 years before
diagnosis. In some sub-groups former OC users faced less risk than nonusers.
 The excess risk of breast cancer diagnoses in OC users was solely for cancers that were
localized. OC users actually had a reduced risk of cancers that had spread beyond the
breast.
 Women who used OCs before age 20 faced somewhat higher relative risk, when
compared with nonusers of the same age, than women who used OCs later in life.
 Whether a woman first used OCs before or after she first gave birth did not appear to
make much difference.
 For women with a family history of breast cancer, OC use did not seem to increase risk
particularly.
 Duration of OC use did not affect risk.
 Data were limited, but risk did not appear to be related to type of estrogen or progestin,
and the only dose-related difference was a reduction in breast cancer among women
who had used the highest dose pills more than 10 years before.
This pattern of findings suggests two possible explanations of a relationship between OC
use and breast cancer. First, OCs may promote the growth of an already existing tumor. The
observations that relative risk is greatest during and soon after OC use and that duration of
OC use has no effect on risk argue that OCs do not initiate new tumors. Second, OC users
may simply have more frequent and more careful breast exams than other women, and thus
their tumors may be found at an earlier stage. The fact that the entire excess risk of breast
cancer diagnosis occurs for tumors that are localized and that OC users actually have a
reduced risk of cancers that are spread beyond the breast strongly supports this possibility.
The Collaborative Group researchers comment: The relation observed between breast
cancer risk and hormone exposure is unusual, and it is not possible to infer from these data
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whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological
effects of hormonal contraceptives, or a combination of reasons.
The finding that the modest additional risk is greatest during OC use and eventually
disappears after a woman stops OCs has important public health implications. Because
most women use OCs when they are young, and breast cancer is extremely rare at young
ages, the number of breast cancer cases attributable to OC use would be quite small. By the
Collaborative Group’s estimate, among 10,000 European or North American women using
OCs from ages 16 to 19, an additional 0.5 cases of breast cancer would be diagnosed in the
10 years after these women quit OC use; among those using OCs from ages 20 to 24, 1.5
additional cases; and among those using OCs from ages 25 to 29, 4.7 additional cases.
Because of this age gradient, earlier OC use in a population does not lead to more cancers
diagnosed overall. Generally, the numbers of additional cases would be smaller in
developing countries, where breast cancer is less common. By 20 years after stopping OC
use, there was no significant difference between women who used OCs at these ages and
nonusers in the cumulative number of breast cancer cases diagnosed.
Further studies of women with a strong family history who have used more recent, lowerdosage formulations of OCs are needed to determine how women with a familial
predisposition to breast cancer should be advised regarding OC use today.
References
1. SHIRLEY, RL. The Breast. In: Gynecology: Principles and Practice. Kistner RW (Ed),
Year Book Medical Publishers, Inc., Chicago and London, pp. 427-437, 1979.
2. CAIRNS J. The treatment of diseases and the war against cancer. Scientific American
253:51-59, 1985.
3. PASQUALINI JR, CHETRITE G. Control of estrone sulfatase activity in human breast
cancer cells: effect of tibolone and its metabolites. Gynecol Endocrinol 11 (Suppl.
1):69-75, 1997.
4. FEBRASGO. Cancer na Mulher. Jornal da Febrasgo 7:07:4-13, 2000.
5. SCHRAG D, KUNTZ KM, GARBER JE and WEEKS JC. Life expectancy gains from
cancer prevention strategies for women with breast cancer and BRCA1 or BRCA2
mutations. JAMA 283:5:617-624, 2000.
6. PARKER SL, TONG T, BOLDEN S, WINGO PA. Cancer Statistics, 1996. Cancer J
Clin 46:5-27, 1996.
7. THOMAS DB. Do hormones cause breast cancer? Cancer 53 (Suppl): 595-604, 1984.
8. ROZENBAUM H. Evolution des conceptions concernant les ralations entre hormones
et pathologie mammaire. Horm. Reprod. Metab. 2:32-39, 1985.
9. BEATSON GT. On the treatment of inoperable cases of carcinoma of the mamma.
Suggestions for a new method of treatment with illustrative cases. Lancet 2:104-107,
1896.
10. BLACKBURN RD, CUNKELMAN JA and ZLIDAR VM. Oral Contraceptives – An
Update. Population Reports, Series A, No. 9, Baltimore, Johns Hopkins University
School of Public Health, Population Information Program, Spring 2000.
11. COLLABORATIVE GROUP ON HORMONAL FACTORS IN BREAST CANCER.
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Suppl.):1-31, 1996.
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