Learning objectives

1. Outline the most appropriate screening and prevention strategy for breast cancer.
2. Describe the most appropriate patient-specific therapy and monitoring for a stage
of disease.
3. Apply the clinical data underlying therapeutic treatment recommendations.
4. Explain expected outcomes to a given therapeutic modality in terms of response
and toxicity or other endpoints (e.g., survival, clinical benefit, etc.).
5. Devise and communicate appropriate plans for preventing, monitoring and
treating adverse reactions associated with treatment of breast cancer.
6. Compare the available bone modifying agents for the management of skeletal-
related events in patients with metastatic breast cancer to the bone.
7. Design an antiemetic regimen for the management of chemotherapy-induced
nausea and vomiting in a patient receiving chemotherapy for breast cancer.
8. Identify anticancer agents that increase the risk of cardiotoxicity in patients with
breast cancer.
9. Create a monitoring plan for patients who have completed adjuvant or
neoadjuvant therapy for early stage or locally advanced breast cancer.
 ANATOMY & PATHOPHYSIOLOGY
• The breast is
comprised of ducts,
lobules, fatty tissue,
other connective
tissues, and
intramammary
lymph nodes.
• Regional lymph nodes include axillary and internal
mammary lymph node chains. Level III axillary lymph
nodes also referred to as infraclavicular.
Supraclavicular also considered regional lymph nodes
in the current AJCC staging system.
 Pathologic types of breast cancer
1. Ductal carcinoma in situ (DCIS) - premalignant lesion; hallmark
clustered microcalcifications on mammogram; usually curable with
resection alone; role of radiation and tamoxifen being studied.
2. Lobular carcinoma in situ (LCIS) - not a premalignant lesion; risk
factor for breast cancer; both breasts are at equal risk; included in
prevention studies with tamoxifen, raloxifene, exemestane, and
anastrozole.
3. Invasive lobular carcinoma (ILC) - second most common type of
breast cancer (15%); more likely to metastasize to serosal surfaces.
4. Invasive ductal carcinoma (IDC) - most common type of breast
cancer (70%); worst prognosis of all types of breast cancer.
5. Others: tubular, mucinous, papillary, medullary; generally have better prognosis
compared to IDC (favorable histologies).
6. Also sarcomas, carcinosarcomas, sarcomatous carcinomas, squamous cell and
others – rare variants with generally poor prognosis.
7. Phyllodes tumor (cystosarcoma phyllodes) – rare tumors comprised of both stromal
and epithelial elements; stratified as benign, borderline and malignant subtypes.
SCREENING & PREVENTION
 SCREENING
Breast self-examination (BSE)
a. Not generally recommended; little data
supporting reduction in mortality when used
alone. May lead to high rates of unnecessary
biopsies.
b. Difficult to separate impact of different
screening tools (BSE, clinical breast exam, and
mammogram); all three should be viewed as
complimentary modalities.
c. If performed, perform monthly; week after
menses.
 Clinical breast examination (CBE)
a. Not uniformly recommended. May be most
beneficial with mammograms (at the same time).
No clinical trial has compared CBE + screening
mammograms to screening mammograms alone.
b. Difficult to separate impact of different screening
tools (BSE, CBE, and mammogram); all three
should be viewed as complimentary modalities.
c. Training of qualified personnel is necessary to
ensure quality of examination.
 Mammography
a. Definite evidence that annual screening
mammography reduces the mortality from breast
cancer in women 50 y/o or older.
b. Data is lacking in women 75 y/o or older. The
decision to stop screening should be
individualized based on the potential benefits
and risk of screening and in the context of overall
health.
c. Women ages 40-49 years:
1) Controversial; many RCT assessing this question.
 Breast MRI
a. ACS guidelines indicate that breast MRI screening is appropriate as
an adjunct to mammography in women with the following (based
on evidence):
1) BRCA mutation carrier.
2) First-degree relative (FDR) of a BRCA mutation carrier, but untested.
3) Lifetime risk ~ 20-25% or greater, as defined by BRCAPRO or other
models largely dependent on family history.

b. Other recommendations based on expert consensus opinion include

the following:
1) Radiation to chest between age 10 and 30 years.
2) Li-Fraumeni syndrome and FDRs.
3) Cowden and Bannayan-Riley-Ruvalcaba syndromes and FDRs.

c. Still controversial in other high-risk groups and for women with a

personal history of breast cancer
Screening Recommendations for Breast Cancer
 Prevention (“risk reduction”)
• 1. Prophylactic mastectomies - decreases risk
by at least 90%.
• 2. Bilateral oophorectomy - decreases
estrogen exposure; decreases risk of breast
cancer by about 50% in carriers of a BRCA 1/2
mutation.
• 3. Primary prevention trials
 Tamoxifen vs placebo
Benefits:
 reduction in incidence of invasive (49%) and noninvasive
 breast cancers (50%);
 reduction in invasive breast cancers in women
 with LCIS (56%) and with atypical hyperplasia (86%);
 Reduced incidence of ER positive tumors, but not ER negative
tumors.
 Reduction in incidence of invasive and noninvasive breast cancers
 persisted with 7 years of follow up.
Risks:
increase in incidence of endometrial cancer (significantly increased in
women ≥ 50 y/o), thromboembolic events (pulmonary embolism
(PE) and deep vein thrombosis (DVT)), significantly increased in
women ≥ 50 y/o), cataracts, hot flashes, and vaginal discharge.
Tamoxifen 20 mg daily vs raloxifene 60 mg daily.
Randomized to 5 years of tamoxifen 20 mg daily or raloxifene 60 mg daily.;
(>35 yo)
Benefits:
similar reduction in incidence of invasive breast cancers (RR 1.02, 95%
CI 0.82-1.28); numerically fewer cases of noninvasive breast cancer with
tamoxifen (RR 1.40, 95% CI 0.98-2.00); no difference in fractures or total
deaths.
Risks:
statistically greater number of patients with endometrial hyperplasia (RR
0.16, 95% CI 0.09-0.29) , VTE (PE + DVT) (RR 0.70, 95% CI 0.54-0.91),
and cataracts (RR 0.79, 95% CI 0.68-0.92) with tamoxifen than raloxifene;
numerically more endometrial cancers and MIs, but these did not reach
statistical significance, probably due to the small number of events.
FDA approved raloxifene for reduction in risk of invasive breast cancer in
postmenopausal women with osteoporosis and in postmenopausal
women at high risk for invasive breast cancer.
 Tamoxifen vs raloxifene
Update with 81 months of follow-up
a) Significant increase in risk of invasive breast cancer in
patients who received raloxifene compared to tamoxifen
(RR 1.24, 95% CI: 1.05–1.47).
b) Numerical increase in risk of non-invasive breast cancers
with raloxifene vs. tamoxifen (RR 1.22, 95% CI: 0.95–1.59).
c) Toxicity greater with tamoxifen vs. raloxifene
i. Uterine cancers (RR 0.55; 95% CI: 0.36–0.83).
ii. VTE (RR 0.75; 95% CI: 0.60–0.93).
iii. Cataracts (RR 0.80; 95% CI: 0.72–0.89) and cataract
surgeries (RR 0.79; 95% CI: 0.70–0.90).
 Aromatase inhibitors (Ais)
Reductions in contralateral breast cancer risk were seen in adjuvant
trials with AIs; 42% reduction in contralateral breast cancers with
anastrozole vs. tamoxifen.
Randomized to 5 years of anastrozole 1 mg PO daily or placebo daily,
median follow-up of 5 years
• Benefits: significant reduction in incidence of invasive and non-
invasive breast cancers favoring anastrozole (2.8% vs. 5.6%, HR
0.47, 95% CI 0.32-0.68); ADH, ALH, and LCIS occurred in 0.2% in the
anastrozole group and 0.5% in the placebo group, HR 0.36, 95% CI
0.11-1.12.
• Risks: musculoskeletal events, arthralgias, carpal tunnel syndrome,
joint stiffness, vasomotor symptoms, dry eyes, vaginal or uterine
prolapse, vaginal dryness, vaginal pruritus, and hypertension were
more common in the anastrozole group; fractures, cardiovascular
events and deaths were not statistically different.
 NCCN Breast Cancer Risk Reduction
Guidelines
• Risk reduction therapy for women with history of
LCIS, 5-year Gail risk ≥ 1.7%, >20% lifetime risk,
pedigree suggestive of genetic predisposition,
known genetic predisposition, prior thoracic
radiotherapy < 30 years of age; life expectancy ≥
10 years; and patient preference for risk
reduction therapy.
• Risk-reducing pharmacologic agents should only
be recommended for women ≥ 35 years of age
 NCCN Breast Cancer Risk Reduction
Guidelines
Options for risk reduction include:

a) Bilateral total mastectomy ± reconstruction

b) Bilateral salpingo-oophorectomy (BSO) with peritoneal washings

(pathologic assessment should include fine sectioning of ovaries and
fallopian tubes).

c) Risk reduction assessment and agents:

i. Baseline gynecologic assessment (for women with intact uterus).
ii. Baseline bone density evaluation (for postmenopausal women).
iii. Premenopausal – clinical trial or tamoxifen.
iv. Postmenopausal – clinical trial, tamoxifen, raloxifene, or AI.
 #1
• TS is a 36-year-old premenopausal white female who
presents with a diagnosis of lobular carcinoma in situ.
She has a significant family history of breast cancer
including her mother, maternal grandmother, and
maternal aunt who were all diagnosed prior to 60 years
of age. TS had one child at age 31 and no history of oral
contraceptive use or estrogen replacement therapy.
She was 12 years old at first menarche.
• What are TS’s risk factors for the development of
invasive ductal carcinoma?
• What are her options for breast cancer risk reduction?
• She declined to undergo genetic testing at this
time.
• Given that she is premenopausal, what are her
breast cancer risk reduction options at this
time?
• What screening options should be
recommended?
• If TS were postmenopausal what would her
options be for risk reduction?
 SIGNS & SYMPTOMS
Usually presents as a painless mass (solitary, unilateral, solid, hard, irregular, and
nonmobile) –90%.
Stabbing or aching pain may be the first symptom – 10%.
Less commonly nipple discharge, retraction, or dimpling may be the first sign.
80% of women first detect some abnormality themselves; detection via screening
mammogram is becoming increasingly common due to increased acceptance and
compliance with routine screening mammography. CBE is routine for verification
when a suspicious area is felt by the px or detected on screening mammography.
For lesions localized to the breast, referred to as early stage breast cancer (usually
includes stage I and II). For lesions that are larger, involve local lymph node basins
or involve the skin or chest wall, referred to as locally advanced breast cancer
(LABC). Inflammatory breast cancer is a unique type of LABC.
Approximately 10% of patients will present with signs and symptoms of distant
metastatic disease; these patients generally have neglected a breast mass for months
to years (result of delayed diagnosis).
Approximately 50% of patients initially diagnosed with non-metastatic breast cancer
will later develop metastases despite multimodality therapy, usually within 3-5 years
following potentially curative therapy.
 DIAGNOSIS & STAGING
• History and physical exam (including a
thorough CBE), diagnostic mammogram (more
detailed than screening), and possibly
ultrasound (US) of breast and lymph node
basins. Biopsy required of an abnormality on
mammogram that is suspicious or of a
palpable breast mass.
• Mammography that was performed at the time of the initial
presentation, 6 years previously, revealed extremely dense breast
tissue but was otherwise normal (A and B).
• Targeted ultrasound evaluation of the palpable mass in the left
breast revealed an irregular, hypoechoic mass, measuring 2.0 cm by
1.8 cm by 0.9 cm (C), which was consistent with cancer.
Pathological examination of the core-biopsy specimen revealed invasive carcinoma. A
lumpectomy of the left breast, with sentinel-lymph-node biopsy and subsequent
axillary-lymph-node dissection, was performed. Examination of the lumpectomy
specimen revealed a tannish-pink irregular mass, measuring 2.5 cm by 2.5 cm by 2
cm; on microscopic examination, the mass was composed of irregular nests of
malignant epithelial cells infiltrating the stroma (A). The tumor cells contained
enlarged, atypical nuclei with distinct nucleoli and showed a moderate degree of
mitotic activity (B). of stromal invasion located less than 0.05 cm from the surgical
margin in the left lateral breast.
The histologic features were hose of a
moderately differentiated, invasive ductal
carcinoma of the breast (grade 2 of 3), with
associated ductal carcinoma in situ (grade 2 to
3 of 3). There was extensive lymphatic
invasion in the surrounding tissue (Fig C). One
axillary sentinel lymph node had evidence of
macrometastatic disease with extracapsular
tumor extension, but an additional 10 axillary
lymph nodes did not have evidence of cancer.
The breast tumor was positive for estrogen
receptor (ER), less than 1% positive for
progesterone receptor (PR), and
negative for human epidermal growth
factor re ceptor 2 (HER2)
overexpression. The hormonereceptor
(HR) status was consistent with a
luminal B genetic subtype of breast
carcinoma. Invasive carcinoma or
ductal carcinoma in situ was located
less than 0.2 cm from several margins.
Reexcision was performed, and
examination of the specimen revealed
multiple foci of lymphatic invasion,
with possible foci
 Diagnosis and staging
• All patients should have a CBC, liver function tests, diagnostic
mammogram (USG if needed), pathologic review, ER/PR/HER2
status, and genetic counseling if at high risk for hereditary breast
cancer. Breast MRI is optional.
• Fertility counseling should be offered to premenopausal women
• For stage I-IIB: Other staging studies are based on signs or symptoms,
and may include a bone scan, computed tomography (CT)/USG/
magnetic resonance imaging (MRI) of the abdomen, or chest CT.
Positron emission tomography (PET)/CT scanning is not
recommended for clinical stage I, II, or operable III breast cancer.
• For stage IIIA-C: Consider a chest CT, CT or MRI of the abdomen
(with or without the pelvis), and bone scan or sodium fluoride
PET/CT. PET/CT may be considered as an optional additional study
for patient with stage III disease (category 2B recommendation).
 How is breast cancer staged?
• The American Joint Committee on Cancer (AJCC) TNM
system

 · The letter T followed by a number from 0 to 4 describes the

tumor's size and spread to the skin or to the chest wall under
the breast. Higher T numbers mean a larger tumor and/or
wider spread to tissues near the breast.
 · The letter N followed by a number from 0 to 3 indicates
whether the cancer has spread to lymph nodes near the breast
and, if so, how many lymph nodes are affected.
 · The letter M followed by a 0 or 1 indicates whether the cancer
has spread/metastased to distant organs -- for example, the lungs
or bones.
TNM Stage Grouping for Breast Cancer
 How is breast cancer treated?
• General types of treatment
• Treatments can be classified into broad groups,
based on how they work and when they are used.
• Local versus systemic therapy
• Adjuvant and neoadjuvant therapy
 additional treatment to help keep the cancer
from coming back.
 chemotherapy or hormone therapy, before
surgery. to shrink the tumor in the hope it will
allow a less extensive operation to be done
 Surgery and radiation
• Lymph node surgery
• Axillary lymph node dissection (ALND): In
this procedure, anywhere from about 10 to
40 (though usually less than 20) lymph
nodes are removed from the axilla (the area
under the arm) and checked for cancer
spread.
• Sentinel lymph node biopsy
(SLNB):removes the first lymph node(s) to
which a tumor drains. This lymph node,
known as the sentinel node, is the one most
likely to contain cancer cells if they have
started to spread.
• To do this, the surgeon injects a radioactive
substance and/or a blue dye into the tumor
or the area around it. Lymphatic vessels will
carry these substances into the sentinel
node(s).

Radiation therapy
 When is chemotherapy used?
• Adjuvant chemotherapy
• Neoadjuvant chemotherapy
• Chemotherapy for advanced breast cancer
• Clinical studies continue to compare today's
most effective treatments against something
that may be better.
 Some of the most commonly used
drug combinations
• CMF: cyclophosphamide (Cytoxan®), methotrexate, and 5-fluorouracil (fluorouracil, 5-FU)
• CAF (or FAC): cyclophosphamide, doxorubicin (Adriamycin®), and 5-fluorouracil
• AC: doxorubicin (Adriamycin) and cyclophosphamide
• EC: epirubicin (Ellence®) and cyclophosphamide
• TAC: docetaxel (Taxotere®), doxorubicin (Adriamycin), and cyclophosphamide
• AC → T: doxorubicin (Adriamycin) and cyclophosphamide followed by paclitaxel (Taxol®) or
docetaxel (Taxotere) [Trastuzumab (Herceptin®) may be given with the paclitaxel or
docetaxel for HER2/neu positive tumors.]
• A → CMF: doxorubicin (Adriamycin), followed by CMF
• CEF (FEC): cyclophosphamide, epirubicin, and 5-fluorouracil (this may be followed
• by docetaxel)
• TC: docetaxel (Taxotere) and cyclophosphamide
• TCH: docetaxel, carboplatin, and trastuzumab (Herceptin®) for HER2/neu positivetumors
Stage IA,IB, IIA, IIB Invasive Breast Cancers (Early
Stage) or T3 N1 M0 (NCCN Guidelines v1.2014)

Goals of therapy: CURE

a. In clinical trials, rates of cure determined by

comparisons of DFS and OS.
b. In individual patients, determined by long-term
survival without recurrence; patient lives a
normal life span and dies of unrelated cause. No
way to prospectively predict who will recur and
who will not.
 #2
• VB is a 58-year-old postmenopausal woman who presents to the clinic
with a newly diagnosed left breast cancer found on screening
mammogram, confirmed by ultrasound and core biopsy. The breast mass
measured 1.2 x 1.1 cm and her axillary lymph nodes were negative by
ultrasound. Core biopsy of the breast mass indicates an invasive ductal
carcinoma, nuclear grade 1 (well differentiated), ER = 55%, PR = 10%,
HER2 IHC = 2, HER2 FISH = normal. All other staging studies were negative
for metastases.
• VB has stage IA disease (T1, N0, M0) that is ER/PR positive, HER2 negative
(ER/PR+, HER2 normal) and well-differentiated. VB elected to have a
lumpectomy with surgical axillary staging. She has negative axillary nodes.
Her pathologic stage is IA (T1,pN0,M0). Her Oncotype DX Recurrence
Score was 20 (intermediate risk of recurrence).
• What systemic therapy would be recommended according to NCCN
guidelines v.1.2018?
• What if VB was premenopausal before starting treatment?
 #3
• GK is a 40-year-old premenopausal woman who presents
to her medical oncologist with a newly diagnosed left
breast cancer found on screening mammogram and
confirmed with ultrasound and core needle biopsy as
invasive ductal carcinoma. The tumor is 4.2 cm x 3.1 cm, ER
negative, PR negative, HER2 IHC 2+, FISH = normal.
Pathology also reveals a nuclear grade of 2 (moderately
differniated) and a Ki-67 of 60%. She recently underwent a
modified radical mastectomy with negative lymph nodes
and negative margins (> 1mm).
• What additional therapy do you recommend?
• What if GK’s disease had been lymph node positive?
 #4
• HF is a 60-year-old healthy female with minimal
comorbidies including hyperlipidemia and
hyperthyroidism. She has a newly diagnosed
Stage IIIb (T4, N2,M0) left breast cancer that is ER
70%, PR 0%, and HER2 IHC 3+. She would prefer a
lumpectomy and radiation; therefore, she must
undergo neoadjuvant chemotherapy with the
hope of decreasing the size of the primary tumor
to allow for adequate surgical resection.
• What neoadjuvant regimen would be most
appropriate?
 #5
PROFIL PASIEN

Data Demografi
Nama :Ny. H Jeniskelamin :Perempuan
Alamat :Jl, abc, Kt Pekerjaan :Ibu RumahTangga
Umur : 31tahun Status Kesehatan : BPJS
Tinggi badan : - BB : 45 kg
MRS: 29 April 2014

Riwayatpenyakit RiwayatOperasi Acute and Chronic Medical Problem

Benjolan diketahui sejak bulan januari 2014,
makin lama makin membesar. Keluar darah dari
puting susu.
Ben
Post operasi pengangkatan
payudara tanggal 10/4/2014
Ca Mammae sinistra stadium IV, infiltrating
Hasil biopsy paska operasi
ductal ca ER- PR- Her2 positif kuat
Infiltrating Dictal carcinoma
dengan ER – PR- Her 2 positif
kuat.
 DATA KLINIK DAN LABORATORIUM
Data Klinik Tanggal
29/4 21/5 11/6 2/7 28/7 19/8
Tekanan Darah 120/80 110/80 110/80 120/80 110/80 110/80
RR 20 16 18 16 20 20
Suhu (°C) Afebris Afebris Afebris Afebris Febris Febris
t = 39 °C t = 38,7 °C
Nadi x/mnt 71 80 76 88 110 108
GCS 456 456 456 456 456 456
Keluhan (-) (-) (-) (-) Sariawan Sariawan

Data Laboratorium Tanggal

29/4 21/5 11/6 2/7 28/7 19/8
Hb (11,4-15,1) 13 12,5 12,8 13,1 11,5 10
Leukosit (4,7-11,3) 5,28 6,23 4,2 3,23 1,23 1,08
Thrombosit (100-400) 200 210 103 116 101 200
MCV 81,5 81 80 81 81 81,5
MCH 28,0 28,5 27,8 28,5 28,5 28,0
MCHC 34,30 34,0 33,4 34,0 34,0 34,30
Ureum (16,6-48,5) 19,60 19,8 20,3 19,60 20,3 19,60
Kreatinin (<1,2) 0,67 0,7 0,8 0,67 0,8 0,67
AST (0-32) 25 26 27 25 27 25
ALT (0-33) 36 35 38 36 38 36
Albumin (3,8-4,4) 3,5 3,2 3,2 3,5 3,2 3,5
CEA <5 11,70 6,5
Ca 15-3 240,32 38,3
Patologi Anatomi Infiltrating ductal Ca
Pengecatan IHK ER – PR – Her 2 Positif
Thoracal Ro Lesi litik multiple di thoracal V sampai VII
 Pengobatan
Obat Dosis Rute Tanggal

29/4 21/5 11/6 2/7 28/7 19/8

Pre Medikasi

Infus Na Cl 0,9% 500 cc IV √ √ √ √ √ √

Ranitidin 50 mg IV √ √ √ √ √ √

Dexamethason 8 mg IV √ √ √ √ √ √

Metoclopramid 10 mg IV √ √ √ √ √ √

Difenhidramin 50 mg IV √ √ √ √ √ √

Palonosentron 0,25 mg IV Drip dalam 100cc NS √ √ √ √ √ √

Docetaxel 110 mg IV Drip dalam 250 cc NS √ √ √ √ √ √

Carboplatin 450 mg IV Drip dalam 500 cc NS √ √ √ √ √ √

Ibandronate 6 mg IV Drip dalam 500 cc NS √ √ √ √ √ √

MST continous 10 mg Po √ √ √ √ √ √
 #5a
• GS is a 62-year-old female who presents with metastatic breast
cancer to the bone. She was originally diagnosed with Stage IIB ER-
negative, PR-negative, HER2 positive (IHC 3+) breast cancer ten
years ago and received treatment with lumpectomy, adjuvant
chemotherapy with TAC x 6 cycles, followed by radiation and one
year of trastuzumab. She has mild bone pain that is controlled with
an NSAID. Biopsy of her recurrent disease is consistent with the
original tumor pathology.
• What systemic therapy would be recommended for her recurrent
disease?
• If GS received docetaxel, trastuzumab, and pertuzumab x 8 months
at which time she developed new metastases in her liver. What
therapy would be most appropriate at this time?
 #6
TY is a 35-year-old premenopausal woman who presents to the clinic with newly
diagnosed right breast cancer measuring 3.0 cm, with a suspicious lymph node in
her axilla (T2, N1, M0). The pathology report indicates invasive ductal carcinoma,
nuclear grade 3 (poorly differentiated), ER = 0%, PR = 0%, HER2 FISH = amplified;
Ki-67 = 80%. Her oncologist would like to administer neoadjuvant chemotherapy.
Which of the following pertuzumab-based regimens is most appropriate based on
the FDA-approved prescribing information?
A. Docetaxel + carboplatin + trastuzumab + pertuzumab for 6 cycles, followed by
adjuvant trastuzumab to complete 1 year
B. Doxorubicin + cyclophosphamide for 4 cycles, followed by weekly paclitaxel for 12
cycles, followed by adjuvant trastuzumab + pertuzumab to complete 1 year
C. Doxorubicin + cyclophosphamide for 4 cycles, followed by weekly paclitaxel +
pertuzumab for 12 cycles, followed by adjuvant pertuzumab to complete 1 year
D. Docetaxel + trastuzumab + pertuzumab for 4 cycles, followed by adjuvant
trastuzumab to complete 1 year
 #7
AO is a 65-year-old postmenopausal woman with stage III
locally advanced breast cancer of the right breast (ER/PR
positive, HER2 normal, nuclear grade 3). Which one of the
following sequences of therapies is most appropriate?
A. Chemotherapy, followed by surgery, followed by radiation
therapy
B. Chemotherapy, followed by surgery, followed by radiation
therapy, followed by endocrine therapy
C. Surgery, followed by radiation therapy, followed by
endocrine therapy
D. Surgery, followed by chemotherapy, followed by radiation
therapy, followed by endocrine therapy
 #8
LG is a 40-year-old premenopausal woman with a history of invasive
ductal carcinoma in the right breast, stage I, ER/PR positive, HER2
normal, nuclear grade 1. The patient underwent appropriate
treatment with surgery and radiation therapy. She recently started
taking tamoxifen, but she is concerned regarding the risk of other
cancers from the long-term use of tamoxifen. According to the most
recent Early Breast Cancer Trialists’ Collaborative Group meta-
analysis, the age group of women taking tamoxifen for 5 years with
the highest risk of developing endometrial cancer is:
A. < 45 years of age
B. 45-54 years of age
C. 55-69 years of age
D. 70 years of age or older
 BONE METASTASES
Incidence is high in patients with advanced cancer
50% of breast cancer patients each year develop
metastases and 65-75% of these patients develop
bone metastases.
Skeletal-related events include:
1. Pathologic fracture
2. Spinal cord compression
3. Surgery to bone
4. Radiotherapy to bone
5. +/- Hypercalcemia
Radiographically lesions are described as osteolytic, osteoblastic or
mixed.

1. Osteolytic lesions (appear less dense on radiographs)

a. Tumor cells activate osteoclast activity without any stimulation of
osteoblastic activity.
b. Parathyroid hormone related protein (PTHrP; secreted by tumor
cells) thought to be important factor in breast cancer bone metastases.
2. Osteoblastic lesions (appear more dense on radiographs)
a. Tumor cells stimulate osteoclasts and osteoblasts with the new bone
formation being deposited in sites unrelated to the resorption cavities.
b. Factors related to osteoblast activation are largely unknown; may be
related to similar mechanisms as seen with PTHrP.
3. Mixed lesions (appear to have features of both osteolytic and
osteoblastic lesions).
a. Most common for patients with breast cancer
 Management
A. ASCO Update on bone modifying agents (BMA) in MBC
Patients with evidence of bone metastases by radiography, CT or MRI (but not only by
abnormal bone scan) should be offered a BMA with concurrent anticancer
treatment.
a. Pamidronate 90 mg IV over at least 2 hours Q 3-4 weeks OR
b. Zoledronic acid 4 mg IV over at least 15 minutes Q 3-4 weeks OR
c. Denosumab 120 mg SQ every 4 weeks.
There is insufficient evidence regarding efficacy to support one bone modifying
therapy over another.
BMA should be continued until evidence of a substantial decline in a patient’s general
performance status.

B. Bisphosphonates
1. Inhibits osteoclast maturation and function – pamidronate and zoledronate
approved for this indication in U.S; others being investigated (e.g., clodronate,
ibandronate).
2. Affinity for bone with exposed minerals (areas of osteolysis).