BREAST CANCER
1.06B
September 7, 2016
Dr. Tia
20 1 8
BREAST CANCER o workup of mammographic abnormalities in the 40-
INCIDENCE EPIDEMIOLOGY to 49-year age group less commonly diagnoses
The most common tumor in women cancer
Men also get breast cancer o about 50% of women who are screened annually
Female:Male ratio = 150:1. during their forties have an abnormality at some point
Hormone-dependent that requires a diagnostic procedure (usually a biopsy),
Reduced risk yet very few evaluations reveal cancer.
o Women with late menarche
o After 13–15 years of follow-up, women who start
o early menopause
o first full-term pregnancy by age 18 screening at age 40 have a small survival benefit.
Women with familial breast cancer more often have false-
RISK FACTORS negative mammograms.
Estrogen replacement therapy - may slightly increase the o MRI - better screening tool in these women.
risk, but the beneficial effects of estrogen on quality of life,
bone mineral density, and decreased risk of colorectal
cancer appear to be somewhat outnumbered by increases in
cardiovascular and thrombotic disease.
Women who received therapeutic radiation before age 30
- increased risk.
Breast cancer risk is increased when sister and mother also
had the disease.
GENETICS
8–10% of breast cancer is familial
BRCA-1
o BRCA-1 mutations account for about 5%.
o BRCA-1 maps to chromosome 17q21 and appears to be
involved in transcription-coupled DNA repair.
o Ashkenazi Jewish women have a 1% chance of having
a common mutation (deletion of adenine and guanine at
position 185).
o The BRCA-1 syndrome includes an increased risk of
ovarian cancer in women and prostate cancer in men.
BRCA-2
o BRCA-2 on chromosome 11 – account for 2–3% of
breast cancer.
Mutations - increased risk of breast cancer in men and
women.
o Germ-line mutations in p53 (Li-Fraumeni syndrome)
rare, but breast cancer, sarcomas, and other
malignancies occur in such families.
o Germ-line mutations in hCHK2 and PTEN may account
for some familial breast cancer.
Sporadic breast cancers show many genetic alterations,
including overexpression of HER2/neu in 25% of cases, p53
mutations in 40%, and loss of heterozygosity at other loci.
DIAGNOSIS and EVALUATION OF BREAST MASSES IN MEN
AND WOMEN
Usually diagnosed by biopsy of a nodule detected by
mammogram or by palpation.
Women should be strongly encouraged to examine their
breasts monthly
Premenopausal women
o questionable or nonsuspicious (small) masses should
be reexamined in 2–4 weeks
o Mass that persists throughout her cycle and any mass
in a postmenopausal woman – should be aspirated.
o If the mass is a cyst filled with non-bloody fluid that goes
away with aspiration - pt is returned to routine
screening.
o If the cyst aspiration leaves a residual mass or reveals
bloody fluid- should have mammogram and excisional
biopsy.
o If the mass is solid - should undergo a mammogram
and excisional biopsy.
Screening mammograms performed every other year
beginning at age 50 have been shown to save lives.
The controversy regarding screening mammograms
beginning at age 40 relates to the following facts:
o Disease is much less common in the 40-to 49-year age
group, and screening is generally less successful for
less common problems
Transcribers: AGBAYANI, DOMINGUEZ, GARCIA, GARANA MANAYON, MENDOZA, MONTEVERDE, SAMAR, SANCHEZ Page 1 of 4
MEDICINE 2
BREAST CANCER
Unless the breast mass is large or fixed to the chest wall,
staging of the ipsilateral axilla is performed at the time of
lumpectomy.
The abnormal mammogram Within pts of a given stage, individual characteristics of the
If a nonpalpable mammographic lesion has a low tumor may influence prognosis:
index of suspicion, mammographic follow-up in 3–6 o improves prognosis
months is reasonable. expression of estrogen receptor
Only about 1 in every 5–10 breast biopsies leads to a o Worsens prognosis
diagnosis of cancer, although the rate of positive overexpression of HER2/neu
biopsies varies in different countries and clinical mutations in p53
settings. high growth fraction
aneuploidy
Breast cancer can spread almost anywhere but commonly
goes to bone, lungs, liver, soft tissue, and brain.
Breast-conserving surgery
o not suitable for all patients
o it is not generally suitable for tumors >5 cm (or for
smaller tumors if the breast is small),
o tumors involving the nipple-areola complex
o tumors with extensive intraductal disease involving
multiple quadrants of the breast,
o for women with a history of collagen-vascular
disease,
o for women who either do not have the motivation
for breast conservation or do not have convenient
access to radiation therapy.
Sentinel lymph node biopsy (SLNB) - standard of care
for women with localized breast cancer and clinically
negative axilla.
SCREENING
It seems prudent to recommend annual or biannual
mammography for women past the age of 40 years.
Screening by any technique other than mammography is not
indicated.
Women that benefit from MRI
o BRCA1 or BRCA2 carriers or untested first-degree
relatives of women with cancer
o women with a history of radiation therapy to the chest
between ages 10 and 30 years
o women with a lifetime risk of breast cancer of at least
20%
o women with a history of Li-Fraumeni, Cowden, or
Bannayan-Riley-Ruvalcaba syndromes
STAGING
Breast cancer subdivision into five subtypes based on gene
expression profiling.
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MEDICINE 2
BREAST CANCER
Operable breast cancer
o Outcome of primary therapy is the same with modified
radical mastectomy or lumpectomy followed by breast
radiation therapy.
o Axillary dissection may be replaced with SLNB to
evaluate node involvement
Sentinel node - identified by injecting a dye in the
tumor site at surgery; first node in which dye
appears.
o Women with tumors <1 cm and negative axillary nodes
require no additional therapy beyond their primary
lumpectomy and breast radiation.
Adjuvant combination chemotherapy
o Premenopausal women with positive lymph nodes
o Pre- and postmenopausal women with negative lymph
nodes but with large tumors or poor prognostic
features
o Postmenopausal women with positive lymph nodes
whose tumors do not express estrogen receptors.
o Added to hormonal therapy in estrogen receptor–
positive, node-positive women and is used without
hormonal therapy in estrogen receptor–negative
node-positive women, whether they are pre- or
postmenopausal.
o The most effective regimen appears to be four cycles of
doxorubicin, 60 mg/m 2 , plus cyclophosphamide, 600
mg/m 2 , IV on day 1 of each 3-week cycle
followed by four cycles of paclitaxel, 175 mg/m 2 , by 3-
h infusion on day 1 of each 3-week cycle.
o Aromatase inhibitors
Estrogen receptor–positive tumors >1 cm with or
without involvement of lymph nodes
Women who began treatment with tamoxifen before
aromatase inhibitors who improved should switch
to an aromatase inhibitor after 5 years of
tamoxifen and continue for another 5 years.
o In premenopausal women, ovarian ablation [e.g., with
the luteinizing hormone–releasing hormone (LHRH)
inhibitor goserelin] may be as effective as adjuvant
chemotherapy.
o Tamoxifen adjuvant therapy (20 mg/d for 5 years)
or an aromatase inhibitor (anastrozole, letrozole,
exemestane) is used for postmenopausal women with
tumors expressing estrogen receptors whose nodes
are positive or whose nodes are negative but with large
tumors or poor prognostic features.
Monoclonal antibodies
o Trastuzumab augments the ability of chemotherapy to
prevent recurrence in women with HER2+ tumors
Breast cancer will recur in about half of patients with
localized disease.
o High-dose adjuvant therapy with marrow support does
not appear to benefit even women with high risk of
recurrence.
TREATMENT Patients with locally advanced breast cancer
Five-year survival rate by stage o Benefit from neoadjuvant combination
chemotherapy (e.g., CAF: cyclophosphamide 500
mg/m 2 , doxorubicin 50 mg/m 2 , and 5-fluorouracil
500 mg/m 2 all given IV on days 1 and 8 of a
monthly cycle for 6 cycles) followed by surgery plus
breast radiation therapy.
Treatment for metastatic disease depends on estrogen
receptor status.
o No therapy is known to cure metastatic disease.
o Randomized trials do not show that the use of high-dose
therapy with hematopoietic stem cell support improves
survival.
o Median survival - 16 months with conventional
treatment: aromatase inhibitors for estrogen
Ductal carcinoma in situ
receptor–positive tumors and combination
o Noninvasive tumor present in the breast ducts
chemotherapy for receptor-negative tumors.
o Treatment of choice: wide excision with breast radiation
o Tumors expressing HER2/neu have higher response
therapy
rates by adding trastuzumab (anti-HER2/neu) to
o Adjuvant tamoxifen - reduced the risk of recurrence
chemotherapy.
Invasive breast cancer
o Some advocate sequential use of active single
o Classified as operable, locally advanced, and
agents in the setting of metastatic disease.
metastatic.
Transcribers: AGBAYANI, DOMINGUEZ, GARCIA, GARANA MANAYON, MENDOZA, MONTEVERDE, SAMAR, SANCHEZ Page 3 of 4
MEDICINE 2
BREAST CANCER
Active agents in anthracycline- and taxane-resistant disease mutations can reduce the risk by 90% with simple
include capecitabine, vinorelbine, gemcitabine, irinotecan, mastectomy.
and platinum agents.
Patients progressing on adjuvant tamoxifen may benefit from
an aromatase inhibitor such as letrozole or anastrozole. Half
of pts who respond to one endocrine therapy will respond to
another.
Bisphosphonates - reduce skeletal complications and may
promote antitumor effects of other therapy.
Radiation therapy - useful for palliation of symptoms.
PREVENTION
Women with breast cancer have a 0.5% per year risk of
developing a second breast cancer.
Women at increased risk of breast cancer can reduce their
risk by 49% by taking tamoxifen for 5 years.
Aromatase inhibitors are probably at least as effective as
tamoxifen and are under study. Women with BRCA-1
Transcribers: AGBAYANI, DOMINGUEZ, GARCIA, GARANA MANAYON, MENDOZA, MONTEVERDE, SAMAR, SANCHEZ Page 4 of 4
