Endocrine: Breast Flashcards
Breast: Anatomy
- The breast extends from the clavicle (approximately
the second rib) to the sixth rib and from the sternum to
the mid axillary line. Approximately 10 to 100 alveoli
(secretory units) form lobules that drain into ducts,
which eventually lead to the nipple. The breast is sur-
rounded by fascia connected by the suspensory liga-
ments of Cooper.
- The blood supply to the breast is mostly from ante-
rior perforating branches of the internal mammary
artery, various branches of the axillary artery, and pos-
terior intercostal arteries. The lymphatic drainage is
primarily to axillary lymph nodes, internal mammary
lymph nodes, and interpectoral nodes of Rotter.
Axillary lymph nodes are stratified into three levels
depending on their location relative to the pectoralis
minor muscle. Level I lymph nodes are lateral to the
muscle. Level II lymph nodes are deep to (behind)
the muscle, and level III lymph nodes are medial to the
muscle (Fig. 14-1).
Breast: Physiology
- The nipple is innervated by T4, no matter how pen-
dulous the breast. Although they do not innervate the
breast, the long thoracic and thoracodorsal nerves are
important because of their proximity to axillary lymph
nodes. Injury to the long thoracic and thoracodorsal
nerves during axillary nodal dissection may result in
winged scapula or weakness in shoulder adduction,
respectively. Additionally, the intercostal brachial cuta-
neous nerves pierce the tail of the breast parenchyma
and, when divided, will cause paresthesias of the medial
aspect of the upper arm.
- Cyclic hormonal changes affect the breast. The
breasts may feel lumpy and tender before menses.
- Pregnancy causes marked hypertrophy of the alveoli,
obules, and ducts in preparation for lactation. With
menopause, the lobules become atrophic.
Breast: Pathology
- Benign conditions of the breast include fibrocystic
changes, fibroadenomas, simple cysts, intraductal papil-
lomas, and gynecomastia. Phyllodes tumors can be
benign, borderline, or malignant. High-risk and prema-
lignant lesions include atypical ductal and lobular
hyperplasia and lobular carcinoma in situ (LCIS). The
most common malignancies are intraductal carcinoma
(also known as ductal carcinoma in situ [DCIS], which
is noninvasive because it does not penetrate the base-
ment membrane), invasive ductal carcinoma, and inva-
sive lobular carcinoma. Inflammatory breast cancer is
characterized by skin involvement (invasion of the
subdermal lymphatics). Paget disease of the nipple is
an intraepithelial neoplasm that may be associated
with an underlying breast cancer (invasive or in situ).
Breast: Epidemiology
- Lifetime risk of American women for developing
breast cancer is one in eight (12%). It is the most fre-
quently diagnosed cancer in women and the second
most frequent cause of cancer-related death among
women. Incidence increases with age and varies among
various ethnic groups: incidence of breast cancer in
Hawaiians is greater than that in Whites, which is
greater than that in Blacks, which is greater than that
in Asians and Hispanics, which is greater than that in
American Indians. Significant risk factors are female
sex, age,
BRCA
gene mutations, hormone replacement
therapy, personal history of breast cancer, radiation to
the chest at age younger than 40 years, first-degree rel-
ative with breast cancer (higher if the relative was pre-
menopausal), and prior biopsy-proven LCIS or atypi-
cal hyperplasia (ductal or lobular). The incidence of
breast cancer in men is 1%. The most common tumor
in young women is fibroadenoma.
Breast: History
- Most women report finding a breast lump while
showering or with breast self-examination. Breast
pain is usually associated with benign lesions, but
may occasionally be present with malignant lesions.
Lumps that increase before menses and decrease after
menses are usually benign simple cysts or fibrocystic
changes. Spontaneous or bloody nipple discharge is
associated with intraductal papillomas. Malignant
lesions do not vary in size with the menstrual cycle.
Patients with advanced stages may have weight loss,
odor from ulcerating or fungating lesions, pain from
bone metastasis (back, chest, or extremities), nausea
or abdominal pain from liver metastasis, or headaches
from brain metastasis.
Breast: Physical Examination
- When examining the breasts, one looks for skin changes,
asymmetry (visible bulge or dimpling of skin), nipple
retraction, palpable masses, and lymphadenopathy in
the axilla and supraclavicular fossa. Well-circumscribed,
mobile, nontender lumps in young women are usually
fibroadenomas or phyllodes tumors. Breast tenderness is
associated with fibrocystic changes or simple cysts.
Vague masses or firm lumps with indistinct borders are
suggestive of malignancy. With advanced stages, there
may be skin changes such as dimpling, peau d’orange
(edema of the skin, making it look like an orange peel),
ulceration, erythema, or fixation to the skin or chest
wall. Enlarged or matted lymph nodes may indicate
metastasis. Paget disease usually presents with nipple or
areolar rash or excoriation. Inflammatory breast cancer
may have erythema, peau d’orange, or skin thickening.
Breast: Diagnostic Evaluation (Part 1)
- With the increase in breast cancer awareness, screening
mammograms initially led to an increase in breast cancer
diagnoses. This increased incidence has subsequently
reached a plateau. Screening mammograms have
resulted in diagnosing breast cancer at an earlier stage,
with improved survival and decreased mortality.
Mammograms miss 15% of palpable breast cancers
and should be done in conjunction with clinical
breast examination. Mammographic signs that suggest
malignancy include a density with indistinct margins,
piculated mass (Fig 14-2), and clusters of or
linear/branching microcalcifications. Lesions not seen
on prior mammograms need further work up. Also, if
the patient reports a palpable lump, then a diagnostic
mammogram (additional views to magnify and/or com-
press the breast are obtained to identify or characterize
the lesion) and breast ultrasound are performed.
Breast: Diagnostic Evaluation (Part 2)
- Ultrasound can differentiate between solid and
cystic masses (Fig. 14-3). It is not optimal for screen-
ing because it rarely detects microcalcifications and is
extremely dependent on the experience of the person
performing the examination.
Breast magnetic resonance imaging (MRI) is rapidly
increasing in popularity. Current indications include
identifying occult primary cancer with axillary metasta-
sis in women with no clinical breast mass and normal
mammogram, screening women at very high risk
(greater than 25%) for developing breast cancer, determining
extent of breast cancer to help with surgical planning,
and measuring response to neoadjuvant therapy.
Advantages of breast MRI include creation of three-
dimensional images, minimal or no breast compression,
effectiveness in women with dense breasts, and high
sensitivity for detecting breast cancer. Disadvantages are
moderate to low specificity (false-positive results lead
to unnecessary biopsies and patient anxiety), expensive
cost, long time to perform examination (30 to 40 min-
utes, as compared with 5 to 10 minutes for mammo-
gram), requirement of contrast, and inability to demon-
strate microcalcifications.
Breast: Diagnostic Evaluation (Part 3)
- Table 14-1 includes the American Cancer Society
recommendations for breast cancer screening.
Lesions suggestive of malignancy on diagnostic
examination are biopsied with image guidance: mam-
mographic, ultrasonographic, or MRI guided core nee-
dle biopsy. Palpable masses not seen with imaging can
be biopsied with fine-needle aspiration (FNA), core
needle biopsy, excisional open biopsy, or incisional
biopsy. A benign lesion can be observed radiographi-
cally and clinically. Malignant lesions require surgical
consultation. If the pathology report shows atypia or
LCIS or is discordant with radiologic or clinical find-
ings, then an open biopsy should be performed. This
may require wire localization by the radiologist. If the
patient presents with skin changes over the breast
mass, an incisional biopsy should be considered, taking
an ellipse of skin with the mass to check for cancer
involvement of dermal lymphatics.
If DCIS or invasive breast cancer is diagnosed patho-
logically, additional pathologic tests are performed. The
umor is checked for hormone receptors, HER-2/neu
receptor, and, occasionally, various other biologic mark-
ers. Tumors with better prognostic indicators are well
differentiated (low-grade cancer), have overexpression
of estrogen receptors or progesterone receptors, and do
not overexpress HER-2/neu receptor. The Oncogene
DX test helps determine whether a woman will bene-
fit from chemotherapy in borderline situations.
Breast: Treatment (Part 1)
- Simple cysts may be aspirated if large or symptomatic.
If the fluid is bloody, it should be sent for cytology to
check for malignancy. If the cyst does not resolve com-
pletely after aspiration or recurs after three aspira-
tions, it should be excised to rule out malignancy.
Solid lumps should be excised if enlarging or
symptomatic or if other diagnostic studies have been
inconclusive (pathology from image-guided biopsy is
discordant with radiographic or clinical findings).
Treatment recommendations for LCIS have evolved
from bilateral mastectomies to the current recommen-
dation of close observation with annual mammogram
and frequent clinical breast examination. LCIS is usu-
ally an incidental finding on a biopsy performed for
other reasons. Although it does increase the risk for
developing subsequent cancer in either breast, it is no
longer thought to be a precursor of breast cancer.
Breast: Treatment (Part 2)
- For intraductal (noninvasive, in situ) or invasive
breast cancers, surgical treatment options are breast-
conserving therapy (lumpectomy with or without radi-
ation therapy) or mastectomy. Lumpectomy is the
removal of the cancer with a rim of normal breast tissue
to obtain clear or negative margins to ensure the cancer
has been completely removed. If there is cancer at the
surgical margin, the patient should undergo re-excision
to obtain clear margins or consider mastectomy.
Mastectomy is the removal of the breast and nipple/
areolar complex (from clavicle to rectus muscle and
sternum to latissimus dorsi, taking pectoralis fascia with
the breast tissue). Statistically, long-term survival is
approximately the same, but local recurrence is slightly
higher with breast-conserving therapy (BCT): 7% to
10% with radiation and up to 25% without radiation, as
compared with mastectomy (3%). If the patient elects
BCT and develops a recurrent cancer in the same breast,
then mastectomy is usually recommended, especially if
the breast has been previously irradiated.
Breast: Treatment (Part 3)
- Although BCT is being performed more often as
a result of earlier stage at diagnosis, there are still
some circumstances when mastectomy should be
recommended: multicentric cancers (cancer in more
than one quadrant of the breast), extensive high-
grade DCIS, large tumor relative to size of breast
where lumpectomy would result in poor cosmetic
outcome, and when clear margins have not been
obtained after re-excision.
In addition, lymph nodes should be checked for
metastasis for staging purposes. Sentinel lymph node
(SLN) biopsy is rapidly replacing the complete axillary
lymph node dissection (CALND) for stage I and II
breast cancer as the standard of care. SLN biopsy
involves injection of a radioactive isotope and/or a vital
blue dye (isosulfan blue or methylene blue) into the
breast (subareolar, intradermal or intraparenchymal) to
locate the first few draining lymph nodes the cancer is
most likely to involve. The “hot” (radioactive) and/or
blue lymph nodes are removed. The axilla is also pal-
pated and any enlarged lymph nodes are also removed.
The average number of sentinel lymph nodes removed
is 2.8. The procedure is 97% accurate. If no SLN is found
or if the SLN has metastasis, then CALND is per-
formed, removing level I and II axillary lymph nodes.
When CALND is performed with mastectomy, the pro-
cedure is called a modified radical mastectomy. The
advantage of SLN biopsy is more intensive pathologic
evaluation of fewer lymph nodes for more accurate stag-
ing and avoidance of lymphedema, which occurs in
approximately 15% of patients who undergo CALND.
Breast: Treatment (Part 4)
- Radiation therapy is most commonly performed
with external-beam irradiation to the breast and may
include the axillary and supraclavicular nodal regions.
Whole-breast radiation usually involves daily treat-
ments over 4 to 6 weeks. Sometimes a boost dose
is given to the lumpectomy site. Interest in partial
breast irradiation has re-emerged with the advent of
the Mammosite balloon. The balloon is inserted into
the lumpectomy cavity and radioactive beads are
implanted into the balloon (similar to brachytherapy).
This permits high doses of radiation to be administered
to the adjacent breast tissue in a shorter period of time
(usually 4 to 5 days). The balloon is subsequently
removed as a minor procedure.
Breast: Treatment (Part 5)
- Antiestrogen hormonal therapy is given to patients if
breast cancer is estrogen or progesterone receptor posi-
tive. It can reduce the risk of recurrence by approximately
50%. Tamoxifen is given to premenopausal women.
Aromatase inhibitors (e.g., anastrozole, letrozole, and
exemestane) are now the recommended hormonal ther-
apy for postmenopausal women because of the lower
incidence of endometrial cancer and thromboembolic
events. However, there is a higher incidence of osteo-
porosis and fractures. Ongoing clinical trials will deter-
mine whether premenopausal women will benefit from
aromatase inhibitors. Sometimes premenopausal women
are treated with chemical or surgical oophorectomy.
Breast: Treatment (Part 6)
- Chemotherapeutic options have also evolved.
Doxorubicin (Adriamycin) and cyclophosphamide is
used predominantly over the combination of cyclophos-
phamide, methotrexate, and fluorouracil. In addition,
taxanes (taxoids) or anthracyclines may be added to
the regimen. Trastuzumab (Herceptin), a monoclonal
antibody, has been shown to improve survival in patients
whose tumors test positive for the HER-2/neu receptor.
Other monoclonal antibody drugs are currently being
evaluated in clinical trials.
Breast: Treatment (Part 8)
- Surgery and radiation therapy are performed for
local control of breast cancer, whereas chemotherapy
and hormonal therapy are initiated for systemic control.
A select group of patients with small, low-grade DCIS
may be treated by lumpectomy without radiation.
Stage 0, I, and II breast cancers are usually treated with
surgery first. The resulting pathology then guides sub-
sequent adjuvant therapy (chemotherapy, hormonal
therapy, radiation therapy, or a combination). Stage III
and IV breast cancers are usually treated with neoadju-
vant chemotherapy (and sometimes hormonal and/or
radiation therapy) followed by surgery and radiation.
Sometimes an advanced-stage breast cancer can be
reduced in size to permit breast-conserving surgery. If
the patient is a candidate, hormonal therapy may also
be given preoperatively (neoadjuvant) or postopera-
tively once the chemotherapy and/or radiation therapy
has finished.
Tables 14-2 and 14-3 show TNM Staging and
American Joint Committee on Cancer Classification
for Breast Cancer, respectively.
As mentioned earlier, screening mammography has
resulted in the diagnosis and treatment of earlier-staged
breast cancers. In addition, improved understanding of
molecular biology of breast cancer has resulted in the
development and use of new hormonal and chemother-
apeutic agents. All of this has resulted in longer survival
rates and lower mortality (Table 14-4).
Breast: Prophylaxis
- In women with breast atypia and LCIS, clinical trials
have shown that tamoxifen decreases the risk of devel-
oping breast cancer. Tamoxifen is usually administered
for 5 years. Some experts postulate that it should be
given longer. The Study of Tamoxifen and Raloxifene
(STAR) trial showed that raloxifene is as effective as
tamoxifen and is associated with 30% fewer throm-
boembolic events and 36% fewer uterine cancers.
For high-risk women who do not want to take
drugs to reduce the risk of breast cancer, an alterna-
tive is prophylactic mastectomy. This reduces the risk
of breast cancer by 97%.
