1044
U N I T 1 1
Genitourinary and Reproductive Function
Proliferative Lesions with Atypia.
Proliferative dis-
ease with atypia includes atypical ductile hyperplasia
and atypical lobular hyperplasia.
57
The hyperplasia
is accompanied by replacement of the normal epithe-
lial cells lining the ducts or lobules with atypical cells
resembling those of carcinoma in situ. The basement
membrane remains intact and, therefore, the cells can-
not metastasize.
There are two types of atypical hyperplasia: lobular
and ductile.
57
Atypical ductile hyperplasia is recognized
by its histologic resemblance to ductile carcinoma in situ
(DCIS). Atypical lobular hyperplasia is defined by pro-
liferation of cells identical to those of lobular carcinoma
in situ (LCIS), but the cells do not fill or distend more
than 50% of the acini within the lobule. Management
of LCIS consists of excisional biopsy. Women with DCIS
are at increased risk for developing invasive cancer or
recurrence of the DCIS lesion. For this reason, DCIS is
evaluated with core-needle biopsy (to be discussed) fol-
lowed by surgical biopsy or excision. Women with both
types of lesions require careful follow-up to prevent and
detect the presence of invasive cancer.
Breast Cancer
Cancer of the breast is the most common female cancer.
Although the breast cancer mortality rate has shown a
slight decline, it is second only to lung cancer as a cause
of cancer-related deaths in women. The decline in the
breast cancer mortality is due to a number of factors,
especially improvements in screening and treatment.
Risk factors for breast cancer include increasing
age, personal or family history of breast cancer (i.e., at
highest risk are those with multiple affected first-order
relatives), history of benign breast disease (i.e., primary
“atypical” hyperplasia), and hormonal influences that
promote breast maturation and may increase the chance
of cell mutation (i.e., early menarche, late menopause,
and no term pregnancies or first child after 30 years of
age). Modifiable risk factors include obesity (particularly
after menopause), physical inactivity, caffeine, moder-
ate to heavy consumption of alcohol, cigarette smoking,
and long-term use of postmenopausal hormone therapy
(especially combined estrogen and progestin).
57
Most
women with breast cancer have no identifiable risk
factors.
Approximately 12% of all breast cancers are heredi-
tary. The probability of a hereditary etiology increases
with multiple affected first-degree relatives, with
women who are affected before 50 years of age, and
those who have multiple cancers.
57
Mutations in two
breast cancer susceptibility genes—
BRCA1
on chro-
mosome 17 and
BRCA2
on chromosome 13—may
account for most inherited forms of breast cancer (see
Chapter 7).
BRCA1
is known to be involved in tumor
suppression. A woman with known mutations in
BRCA1
has a lifetime risk of approximately 57% for
breast cancer and approximately 40% for ovarian can-
cer.
BRCA2
is another susceptibility gene that elevates
lifetime breast cancer risk to 49% and ovarian cancer
risk to 18%.
59,60
Breast cancer risk reduction options
available to known carriers of
BRCA1
and
BRCA2
mutations include surveillance and surgery. Breast eval-
uation using MRI, digital mammography, and breast
ultrasound give the best sensitivity for detecting breast
cancer. Prophylactic surgery, in the form of bilateral
mastectomy, bilateral oophorectomy, or both, has been
shown to decrease the risk of developing cancer. These
controversial surgeries can have physical and psycho-
logical side effects that warrant careful consideration
before proceeding.
Detection
Cancer of the breast may manifest clinically as a mass,
a puckering, nipple retraction, or unusual discharge.
Many cancers are found by women themselves—some-
times when only a thickening or subtle change in breast
contour is noticed. The variety of symptoms and poten-
tial for self-discovery underscore the need for all women
to have an awareness of what their normal breast
appearance and texture are like.
Mammography is the only effective screening tech-
nique for the early detection of clinically inapparent
breast lesions. A generally slow-growing form of cancer,
breast cancer may have been present for 2 to 9 years
before it reaches 1 cm, the smallest mass normally
detected by palpation. Mammography can disclose
lesions as small as 1 mm and the clustering of calcifica-
tions that may warrant biopsy to exclude cancer.
In 2003, the American Cancer Society dropped its
recommendation that all women perform regular, sys-
tematic breast self-examination (BSE). Research has indi-
cated that most women who discover their own cancer
do so at times other than scheduled BSE. The American
Cancer Society screening guidelines now place primary
emphasis for breast cancer diagnosis on clinical breast
examination (CBE) by a trained health professional and
mammography, while encouraging women in the area
of self-awarenenss.
21
Between the ages of 20 and 39
years, average risk women should undergo CBE every
3 years, and after age 40 years CBE should take place
annually, ideally prior to the woman’s annual mammo-
gram.
21
There is no specific upper age at which mam-
mogram should be discontinued. Instead it is suggested
that decision to stop mammogram screening should be
individualized based on the potential risks and benefits.
As long as the woman is in good health and would be a
candidate for cancer treatment, it is recommended that
she continue to be screened with mammography.
21
Diagnosis and Classification
Procedures used in the diagnosis of breast cancer include
physical examination, mammography, ultrasonography,
percutaneousneedleaspiration,stereotacticneedlebiopsy
(i.e., core biopsy), and excisional biopsy. Figure 40-19
illustrates the appearance of breast cancer on mam-
mography. Breast cancer often manifests as a solitary,
painless, firm, fixed lesion with poorly defined borders.
It can be found anywhere in the breast but is most com-
mon in the upper outer quadrant. Because of the vari-
ability in presentation, any suspect change in breast
tissue warrants further investigation. The diagnostic
