OBSTETRICS & GYNECOLOGY
DANIELA CONTAGE SICCARDI, MD
Breast
Cancer
At the present rate of incidence, one of every 9 American women will
develop breast cancer during her lifetime. 43.000 women die each year
of the disease. The carcinoma of the breast is still the most common
invasive cancer in women from the ages of 15-54, and the second most
common cause of death in the age group 55-74.
"It is both ironic and tragic that a neoplasm arising in an exposed
organ, readily accessible to self-examination and clinical diagnosis,
continues to exact such a heavy toll." ( Robbins,1994,p1099).
I-Risk Factors:
genetic predisposition- the risk is 1.5 to 2 times for women with
one first-degree relative with breast cancer and 4 to 6 times for those
with two affected relatives. It is important to say, however, that
there is no history of breast cancer among female relatives in over 90%
of patients with breast cancer.
increasing age - uncommon before 25, but a steady-state to the time
of menopause, followed by a slower rise throughout life.
length of reproductive life - risk increases with early menarche
(<12 years) and late menopause(>50 years).
parity - more frequent in nulliparous.
age at first child - increased risk when older than 30 years of age
at time of first child.
exogenous estrogens - moderately increased risk with high-dosage
therapy for menopausal symptoms.
oral contraceptives - no clear-cut increased risk.
obesity - increased risk attributed to synthesis of estrogens in
fat depots.
geographic influences - more common in the developed Occident.
fibrocystic changes - the risk is 1.5 to 2 times for moderate
epithelial hyperplasia, sclerosing adenosis and papilloma. 4 to 5
times for ductal and lobular atypical hyperplasia, and 8 to 10 times for
lobular and ductal carcinoma "in situ".
carcinoma of the contra-lateral breast or endometrium - increased
risk.
II- Pathogenesis
Carcinogenesis of the breast is a sequential mechanism that can be
divided into 3 phases:
induction phase - It depends on the action of carcinogenic factors
(genetic duplication errors, chemical agents, viruses and radiation)on
probably one single cell, altering its DNA, changing cellular cycle
control and making a modified cellular clone. The genetic factors
involved can be subdivided in: activation of proto-oncogenes and loss
of the gene supressors blockade.
Some genetic processes like amplification and mutation, can
transform proto-oncogenes into oncogenes, which stimulates cellular
growth and multiplication in such an abnormal manner. The principal
oncogenes known are: c-erb B2, c-myc, int-2 and ras.
On the other hand, we have the gene supressors, trying to block
cellular multiplication. They are represented by: BRCA 1, BRCA 2 and
p53. BRCA 1, when mutated, is related with breast and ovarian cancers.
This gene plays an important role in familiar cases, which correspond to
5 to 10% of all cases of breast cancer. Mutations on BRCA 2 are related
with early breast cancer and also carcinoma of the breast in men. The
other gene, p53, codifies for the synthesis of a phosphoprotein named
p53, which is an important modulator of the cell cycle. It acts
blocking cellular division every time there is an altered DNA.
promotion phase - Once we have genetic modified cells, they start to
multiplicate, influenced by growth promoters and inhibitors. The speed
of this process depends on the doubling time of each tumor. The
doubling time of breast cancer cells ranges from several weeks, in a
rapidly growing lesion , to nearly an year , in a slowly growing one.
If one assumes that the rate of doubling is constant, and that the
neoplasm originates in one cell, a carcinoma with a doubling time of
100 days may not reach clinically detectable size (1cm) for about 8
years.
It seems that we have two critical periods for breast cancer
promotion: the first one between 10 years of age and first pregnancy,
in the time of breast development, when a proliferative estimulation is
found. The second one is in the moment of breast involution, the
perimenopause, when an epithelial tissue atrophy must occur. It is
believed that a hormonal imbalance on these periods could alter the
dynamics of the organ, stimulating proliferative activity and
promoting tumor growth.
Some growth promoters known are: steroid hormones, inflammation and
growth factors like EGF(Epithelial Growth Factor) and TGF-a
(Transforming Growth Factor). The presence of these factors is
associated with the super-expression of some oncogenes, like
c-erbB2.
In this phase, breast can also be influenced by inhibitor factors,
just like pregnancy. Such protection is related to placental hormones
like chorionic gonadotropin and estriol.
progression phase - At this point we have a tumor with capacity of
invasion and metastatization. Host defenses try to block the evolution
of the process, specially through natural killer cells. We have also
biomodulators , like TGF- , trying to inhibit the development of
malignant cells. Without therapeutic measures , however, invasive cancer
metastasizes, involving more commonly bones, lungs and liver.
III - Diagnosis
a) Self-examination - 90% of the breast masses are discovered by
the patient herself. From this manner, self-examination appears as one
of the most important measures for the early diagnosis of breast
cancer, once it: allows the detection of small masses; is an useful,
convenient, profitable, advantageous and opportune method: can be
repeated as many times as necessary; has no cost; is easy to be
done; its precision increases with practice.
A trial made in Finland (1980) confirmed the efficacy of
self-examination, through the following data: the number of new cases
detected per year almost duplicated; the mean age of diagnosis once
between 55 and 64 , lowered to 35 to 44 ; the global survival rate in 5
years that was 55%, increased to 69%.
Self-examination must be performed mensally ( preferably 7-8 days
after menstruation) by every woman with more than 20 years old, in order
to detect early changes in breast parenchyma .
b) History - Verify the presence of risk factors and evaluate the
patient’s complaint
Risk Factors - sex ( 100 women : 1 men); familiar history; adverse
hormonal environment; other lesions on the breast in the past
Presenting Complaint - lump - is the main complaint ( 70% of the
cases). Evaluate its consistence , mobility, growth, changes with
menstrual cycle, and if it is painless or not .
nipple discharge - investigate spontaneous discharge, which can be
watery, serous or bloody. Remember some medications can cause nipple
discharge, such as contraceptives and reserpine.
eczema - if it is important, unilateral and in the nipple area, it
can suggest the presence of malignancy in the ductal system below the
nipple.
pain - especially if after menopause and if unilateral .
other - erosion, retraction, enlargement, swelling, redness, axillar
mass and bone pain .
c) Physical Examination - Inspection of the breast is the first
step in physical examination and should be carried out with the patient
sitting, arms at sides and then overhead. Abnormal variations in breast
size and contour , minimal nipple retraction, and slight edema, redness
or retraction of the skin can be identified. Asymmetry of the breasts
and retraction or dimpling of the skin can often be accentuated by
having the patient raise her hands overhead or press her hands on her
hips, in order to contract the pectoralis muscles . Axillary and
supraclavicular areas should be thoroughly palpated for enlarged nodes
with the patient sitting. Palpation of the breast should be performed
with the patient both seated and supine with the arm abducted.
Every woman between 20-40 years must have her breasts examined by a
specialist every 2/3 years. After 40 years, examinations must be
annually , and in women with high-risk for breast cancer, every
semester.
d) Mammography - It is the single reliable means of detecting breast
cancer before a mass can be palpated in the breast ( it can detect
microcalcifications smaller than 1mm of diameter, and frequently
associated with malignant lesions).
Over then for screening, indications for mammography are as follows:
to evaluate each breast when a diagnosis of potentially curable breast
cancer has been made; to evaluate a questionable or ill-defined breast
mass or other suspicious change in the breast; to search for an
occult breast cancer in a woman with metastatic disease in axillary
nodes or elsewhere; to screen a group of woman with high risk for
breast cancer; to screen women prior to cosmetic operations or prior
to biopsy; to follow women who have been treated with breast-conserving
surgery and radiation.
Patients with a suspicious mass must have a cyto/hystological exam
made, despite mammographic findings . Mammography IS NOT a substitute
for biopsy!
The American College of Radiology and The American Cancer Society
recommend a baseline mammogram on all women between the ages 35 and 40
years. Women aged 40-49 years should have a mammogram every 1-2
years. Annual mammograms are indicated for women age 50 years or
older. High risk women should have an annual mammogram and biannual
examinations.
e) Ultrasound - US can distinguish between solid and cystic lesions
, although it is less sensitive than mammography in identifying breast
cancer, especially because neoplastic areas are difficult to be
differentiated from normal parenchyma. On the same way, it is
difficult to differ from malignant and benign characteristics.
Isolated US can rarely detect malignant lesions smaller than 1 cm or
microcalcifications. It is generally used to evaluate young women’s
(<35 years) breasts, once mammograms are not indicated in these
cases.
f) Cytology - Fine Needle Aspiration (FNA) has a simple technique
and a high level of concordance with hystopatological findings. The
cyto/hystopathologic relation is 83.4%, but in malignant lesions this
relation is 94.7%. It is important, however, to say that FNA results
are ONLY diagnostic when concordant with clinical findings! Axillary
nodes can also be examined, in order to stage disease.
g) Biopsy - It is the preferred isolated diagnostic method before
deciding on a definite treatment. Delayed biopsy must be preferred to
frozen biopsy, once it: allows patients to accept their diagnosis, to
decide on their treatment, and even to look for a second opinion.
Trials have been demonstrating that there is no problem in delaying
treatment for 1-2 weeks with this routine, and this is the actual
recommendation of the National Institute of Cancer in America.
IV - Differential Diagnosis - It includes , in decreasing order
of frequency: fibrocystic changes, fibroadenoma, intraductal papilloma,
duct ectasia, and fat necrosis.
Bibliography
1 - Robbins, Pathologic Basis of Disease, 5th Edition
2 - Goroll, Primary Care Medicine
3 - DeCherney & Pernoll, Current Diagnosis and Treatment of
Gynecology and Obstetrics
4 - Benson and Pernoll, Handbook of Obstetrics and Gynecology, 9th
Edition
If you have suggestions or comments send an e-mail to Daniela Contage Siccardi
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