Breast cancer
Amsalu Degu
(B.Pharm, M.Pharm in Clinical Pharmacy, MSc in Pharmacology)
USIU-Africa
School of Pharmacy and Health Sciences
1
Objectives
• At the end of this session, the students are expected to:
 List factors associated with an increased risk of breast cancer
 understand the histological classification of breast cancer
 Assess patients for signs and symptoms related to breast cancer in early and
late stages of the disease
 understand the TNM staging of breast cancer
 Determine the treatment goals for early-stage, locally advanced, and
metastatic breast cancer.
 Determine appropriate indications for endocrine therapy, chemotherapy, and
biologic therapy for patients with breast cancer
 Identify monitoring parameters
2
Introduction
• Breast cancer is a malignant proliferation of
epithelial cells lining the ducts or lobules of the
breast
• Starts when cells in the breast begin to grow out
of control
• Most breast cancers begin in the ducts that carry
milk to the nipple (ductal cancers).
• Some start in the glands that make breast milk
(lobular cancers)
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Epidemiology
• 2nd leading cause of cancer death in women,
exceeded only by lung cancer.
• The disease occurs almost entirely in women,
but men can get it, too
• The left breast is involved more frequently
than the right
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Epidemiology
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Risk factors
• The exact etiology is unknown
• Age
– incidence increases with age
– median age diagnosis is b/n 60-65 years
• Gender
– females have higher incidence than males
• Genetics
– BRCA1, BRCA2, p53 mutation
• A family history of breast cancer
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Risk factors
• Endocrine factors (prolonged exposure to
estrogens)
– Early menarche< 12 years
– Nulliparity
– Late menopause ≥ 55years
– Late age at first full term birth ≥ 30yrs
– long term use of hormonal replacement
therapy
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Risk factors
• Environmental & lifestyle factors
– Diet- Increased fat & caloric intake
– Obesity-Increased free circulating estrogen
– Smoking
– Alcohol
– Reduced physical activity
– Radiation in younger women <30yrs
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Case study: Risk factors
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Histological classification
• Invasive carcinoma
– Ductal
• the most common (80%) type of breast
invasive ductal carcinomas
• Starts in a milk duct of the breast
• Lobular
–Starts in the milk-producing glands
(lobules)
• Non-invasive carcinoma: ductal or lobular
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Types of Breast Cancer
• Endocrine receptor-positive (ER and PR)
– About 80% of all breast cancers are “ER-positive
• HER2-positive
– aggressive and fast-growing
– Accounts for 20% of breast cancers
• Triple positive
– positive for ER, PR and HER2
• Triple negative
– not positive for ER, PR & HER2
– more common in younger women
– grow & spread faster than most other types of breast
cancer
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Types of breast cancer
• About 50-70% of patients with primary or
metastatic breast cancer have HR- positive tumors
• HR positivity
– Associated with a superior response to
hormone therapy
• HR positive tumors are more common in
postmenopausal patients than in premenopausal
patients
• HR positive cancers tend to grow more slowly
than HR-negative
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Clinical Presentation
• Common early symptoms
– painless lump (90% of cases) that is typically
solitary, unilateral, solid, hard and irregular.
– Stabbing or aching pain (10% of cases)
• Uncommon early symptoms
– Nipple discharge (3% of women & 20% of
men)
– Eczema appearance of the nipple
– Prominent skin edema, redness, warmth, and
induration of the underlying tissue
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Clinical Presentation
• Metastatic symptoms
– Bone pain
– Difficulty breathing
– Abdominal enlargement
– Jaundice
– Mental status changes
– Tissues most commonly involved with
metastases are lymph, skin, bone, liver, lungs,
and brain
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Clinical Staging
• Stage I
 represents small primary tumor without lymph node
involvement
• stage II
 the majority of disease involves regional lymph nodes
 Stages I and II are often referred to as early breast
cancer. It is in these early stages that the disease is
curable.
• Stage III
 also referred to as locally advanced disease
 usually represents a large tumor with extensive nodal
involvement in which either node or tumor is fixed to the
chest wall.
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Clinical Staging
• Stage IV
– is characterized by the presence of
metastases to organs distant from the primary
tumor
– is often referred to as advanced or metastatic
disease
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Screening: American Cancer Society recommendations
• Women age 40-44
– should have the choice to start annual breast cancer
screening with mammograms if they wish to do so
• Women age 45-54
– should get mammograms every year
• Women 55 and older
– should switch to mammograms every 2 years, or can
continue yearly screening
• Average risk women
– if she doesn’t have a personal history of breast cancer,
a strong family history of breast cancer, or a genetic
mutation known to increase risk of breast cancer
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Screening
• Individuals considered high risk
– Have a known BRCA gene mutation
– Untested for the BRCA gene mutation but have a
first-degree relative with a BRCA mutation
– Have a strong family history of breast cancer
– For screening: Annual mammography & breast
MRIs should be initiated starting at the age of 30
years
– Screening with breast MRI is recommended in highrisk individuals.
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Diagnosis
• Triple assessment of any symptomatic breast
mass by
– Palpation
– Radiology (mammography, ultrasound and
MRI scan)
– Fine-needle aspiration cytology
– Virtually all breast cancer is diagnosed by
biopsy of a nodule detected either on a
mammogram or by palpation
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Prevention
M.P. should include information on both tamoxifen and raloxifene in
her talk.
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Prevention
• Surgery (prophylactic mastectomy)
– Women who are considered high risk for
breast cancer may decide to undergo
prophylactic
mastectomy
with
reconstruction
• Chemoprevention
– Two agents approved for prevention are
tamoxifen (20mg/day*5yrs)& raloxifene (60
mg daily*5yrs)
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Management
• Treatment is stratified according to the extent
of the disease
– Surgery
– chemotherapy
– Radiotherapy
– hormonal therapy
– biological agents
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Treatment: early breast cancer (stage I & II)
• Goal of therapy
– Curative
• Surgery alone can cure most
– modified radical mastectomy (total
mastectomy with ipsilateral axillary lymph
node dissection)
– Breast-conservation therapy (lumpectomy
& 4-6weeks radiation therapy)
• All patients with stage II breast cancer should
be considered for systemic adjuvant therapy
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Radical mastectomy
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Lumpectomy
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Treatment: locally advanced breast cancer (stage III)
• locally advanced breast cancer
– Refers to breast carcinomas with significant
primary tumor & nodal disease
• consists of a combination of surgery, radiation &
chemotherapy administered in an aggressive
approach
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Treatment: locally advanced breast cancer (stage III)
• Goal of therapy
– to cure the disease
• initial approach to therapy should be chemotherapy
with the goal of achieving resectability
• Neoadjuvant chemotherapy
– most tumors respond with >50% decrease in
tumor size
– Chemotherapy regimens are similar to those used
in the adjuvant setting
– most of the available data support the use of
anthracycline containing regimens
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Treatment: locally advanced breast cancer (stage III)
• Neoadjuvant endocrine therapy
– may be an option for patients HR-positive
tumors who are unable to receive
chemotherapy (e.g.,multiple comorbid
conditions)
• Adjuvant radiation therapy
– should be administered to all locally advanced
breast cancer patients to minimize local
recurrences regardless of the type of surgery
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Treatment: metastatic breast cancer (stage IV)
• Goal of treatment
– to improve symptoms, maintain quality of life
& extend survival
• important to choose therapy with good activity
while minimizing toxicities
• Can be treated with
Hormonal therapy (preferred if HR +ve)- first line
and second line
Systemic cytotoxic agents for hormone refractory
disease
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Palliation of metastatic breast cancer
• Palliative Surgery
– Commonly offered to patients with brain
metastases, spinal cord compression, fractures,
or symptomatic pleural or pericardial effusions
not controlled by other means
Palliative radiation
– Offered to patients with bone metastases, brain
metastases, spinal cord compression
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Adjuvant chemotherapy regimens in nodepositive breast cancer
• Chemotherapy is usually initiated within 3
weeks of surgical removal of the primary
tumor
• The basic principle of adjuvant therapy
– The regimen with the highest response rate
in advanced disease should be the optimal
regimen for use in the adjuvant setting
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Adjuvant Endocrine therapy
• Goals of therapy
– to decrease circulating levels of estrogen
and/or
– to prevent the effects of estrogen at the breast
cancer cell (targeted therapy) through
blocking the hormone receptors
• combinations have not demonstrated any
efficacy benefits but have increased toxicity
39
Adjuvant Endocrine therapy
•
•
•
•
Antiestrogens: Tamoxifen
oophorectomy
ovarian irradiation
luteinizing hormone–releasing hormone
(LHRH) agonists: Goserelin, Leuprolide
• aromatase inhibitors: Anastrozole, Letrozole
Exemestane
40
Adjuvant Endocrine therapy
• Tamoxifen
– was the “gold standard” adjuvant hormonal
therapy
– antiestrogenic in breast cancer cells
– have estrogenic properties in other tissues
and organs
– can be used in both premenopausal &
postmenopausal women with metastatic
breast cancer who have tumors that are
hormone-receptor-positive
41
Adjuvant Endocrine therapy
• Aromatase inhibitors
– Effectively reduce the level of circulating
estrogens, as well as estrogens in the target
organ.
– a standard of care for postmenopausal women
with HR positive early stage & metastatic
breast cancer
– Treatment duration: for five years
• because there is no data to support the
benefit of extended treatment beyond this
duration
42
Adjuvant Endocrine therapy
• Early studies
– found no benefit to taking tamoxifen for more than the
standard 5 years
• Recent studies
– found that taking tamoxifen for 10 years lowered
recurrence rates, reduced breast cancer risk in the
opposite breast, and improved survival
• postmenopausal women have been able to take an aromatase
inhibitor instead of tamoxifen, but they can take either
medicine.
• aromatase inhibitor do not work in premenopausal women
43
• According to American Society of Clinical Oncology
(ASCO) guideline
– women postmenopausal after 5 years should be
offered continued tamoxifen for up to 10 years, or
switch to up to 5 years of an AI
– If postmenopausal at start of hormonal therapy,
women should be offered
– tamoxifen for 10 years, or
– AI for 5 years, or
– tamoxifen for 5 years, then switch to AI for up to 5
years, or
– tamoxifen for 2 to 3 years, then switch to AI for up
to 5 years
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Endocrine Therapies Used for Metastatic Breast Cancer
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Chemotherapy regimens: metastatic breast
cancer
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Adjuvant Biologic Therapy: Trastuzumab
• a monoclonal antibody directed against the
HER-2/neu receptor
• The overexpression of HER-2/neu is
associated with increased transmission of
growth signals that control aspects of cell
growth & division
• Indicated for treatment of adjuvant &
metastatic breast cancer in patients who have
tumors that overexpress HER-2/neu
48
Adjuvant Biologic Therapy: Trastuzumab
• should not be given concurrently with the
anthracyclines because of an increased risk of
cardiotoxicity
• Baseline and every 3 months cardiac function tests are
required during treatment
• Side Effects
– Infusion reactions (fever, chills, rigors), nausea,
vomiting
– pain at tumor site , headaches, dizziness, dyspnea
– hypotension, heart failure
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Bisphosphonates adjunct therapy
• Recommended in breast cancer metastasized to
bone to reduce bone pain and fractures
• Pamidronate (90 mg) & zoledronate (4 mg) can
be given IV once each month
• given in combination with calcium & vitamin
D
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Management of male breast cancer
• Investigation is identical to that of the female
patient
• The majority of male breast cancers are
hormone-positive
– candidates for adjuvant endocrine therapy.
• For most men with breast cancer, tamoxifen is
the preferred agent
52
Prognostic factors for breast CA
• Patient age
– Patients diagnosed at age younger than 35
years have a worse prognosis.
• Tumor size
– In general, patients with a larger tumor have
a worse prognosis
53
Prognostic factors for breast CA
• Lymph node involvement
– Patients with node-positive disease have a
worse prognosis.
• Hormone-receptor status
– Patients with ER & PR negative tumors
have a worse prognosis.
• HER-2/neu protein expression
– Patients with HER-2/neu over expression
have a worse prognosis
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Monitoring parameters
• Early & locally advanced breast cancer
– Physical examination to detect breast cancer recurrence
– Annual mammography
– Symptom-directed work-up
• Metastatic breast cancer
– patients are monitored monthly for signs of disease progression or
metastasis to common sites, such as the bones, brain, or liver
– Pain
– Mental status or other neurological findings
– Laboratory tests
• Liver function tests
• Complete blood count
• Calcium, electrolytes
• tumor markers: CA 15-3, CA 27-29, CEA
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Case study: breast cancer
• C.D. has two first-degree relatives with early-age breast cancer.
• This would indicate an inherited genetic mutation.
• Genetic testing for the presence of BRCA1 and BRCA2 mutations should be
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discussed with C.D.
Case study: breast cancer
• What are the typical signs and symptoms of
breast cancer and does C.D. have any?
– C.D. had a painless lump identified on
mammogram
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Case study: breast cancer
• C.D. will need to undergo a biopsy and full staging
with a CT scan of the chest, abdomen, and pelvis
and a bone scan
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Case study: breast cancer
• Invasive ductal carcinoma is the most common
type
• have stage II disease based on the size of her
disease and the involvement of ipsilateral
lymph nodes.
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Case study: breast cancer
Size of the tumor, lymph node involvement, Pathologic
testing of the breast tumor (ER and PR and HER2 status)
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Case study: Breast cancer
• C.D. could either undergo breast-conserving surgery plus
radiation therapy or a modified radical mastectomy
• But with C.D.’s family history she may also choose to undergo
bilateral mastectomies to prevent the development of
contralateral breast cancer.
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Case study: Breast cancer
• Based on this information, C.D. would be a
candidate for surgery & chemotherapy (based
on the tumor size and lymph node–positive
disease), followed by hormonal therapy due to
her ER/PR-positive disease.
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Case study: breast cancer
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Case study: breast cancer
C.D. should be counseled on the common toxicities associated
with her chemotherapy, such as myelosuppression,
nausea/vomiting, alopecia, neuropathy, cardiomyopathy, and
hypersensitivity reactions
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Case study: breast cancer
• C.D. is premenopausal, so she would start with
tamoxifen therapy
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