Breast Cancer Flashcards
Breast Basics:
• Breast develops in the fatty layer
on the front of the chest.
• Each breast consists of 15-20
lobes
• Each lobe connects to ducts.
• Ducts lead to the nipple
• Not all breast lumps are cancer
• Up to 90% of breast lumps are
NOT cancer
• Cancer can occur in:
• Ducts (most common)
• Lobules (second most
common)
• Other areas (rare)
Risk Factors
• Increasing Age
• Risk doubles between ages of 45 and 65
• Female sex > Male sex
• Personal history (previously diagnosed with breast ca increases risk of additional breast cancers)
• Family history
• mother, sister, daughter diagnosed with breast cancer increases risk 2-9 times
• Estrogen Exposure
• Endogenous (menarche before 12 y/o, menopause after 55 y/o, nulliparity of first pregnancy at >30y/o)
• Exogenous: (History of HRT after menopause or HRT > 5 years)
• Radiation exposure to chest at a young age (example survivors of childhood lymphoma or pilots)
• Alcohol consumption: linear relationship of increased consumption with increased risk
• Obesity: in postmenopausal women, obesity associated with increased breast cancer mortality
• Dense breast tissue – increase breast cancer risk and more difficult to detect cancer on mammogram
• Breastfeeding REDUCES the risk of breast cancer
Genetics Risk Factors
• Family History
• Germline mutations: BRCA1 and BRCA2
• BRCA1 and BRCA2 stand for breast cancer susceptibility gene 1 and breast cancer susceptibility gene 2, respectively
• Both are tumour suppressor genes (prevent uncontrolled cell growth)
• BRCA1 and/or BRCA2 mutations account for approximately 10% of breast cancers
• Those who have BRCA1 mutation have a 50 – 70% chance of developing breast cancer before age 70 and those with BRCA2 mutation have a 40 – 60% risk by age 70.
• Normally these mutations are rare. However, they are more common in people with Ashkenazi Jewish ancestry (1 in 40)
• Several other rare germline genetic conditions can increase risk
• Example: Li-Fraumeni syndrome with inherited mutation in the TP53 gene, which is normally a tumour suppressor gene.
Risk Factor Myths:
• Breast implants
• The implants themselves do not increase risk of breast cancer
• However, it is more difficult to perform mammograms on women with implants (more difficult to screen)
• Oral Contraceptives (controversial)
• Generally OC’s do NOT increase cancer risk. Perhaps a small increased risk in women who
have taken older types of oral contraceptives with a higher estrogen content
• Underwire bras
• Do not cause cancer
• Mammograms
• Do not cause cancer
• Antiperspirants/deodorants
• Currently no reliable evidence to show that antiperspirant or deodorant increased risk of
breast cancer
Breast Cancer Screening
• Mammogram
• X-ray of the breast
• Screening Mammogram
• Regular checks used to find early signs of
cancer in women with no noticeable breast
problems or symptoms
• Can miss up to 10% of breast cancer
• Diagnostic Mammogram
• More images than a screening mammogram.
• Closer look at a specific area of concern (ex:
lump, dimpling, nipple discharge)
• Note that often times, an area of concern is
imaged with ultrasound (U/S) instead of, or
in addition to, a diagnostic mammogram
Breast Cancer Screening in Alberta
women 40-49: less clear that benefits outweight risks, talk to healthcare provider
women 50-74: mammogram screening recommended every 2 years
LGBTQ2S+ Breast/Chest Cancer Screening
• Person with breast tissue
• Regular breast/chest screening recommended
(including persons taking testosterone and
persons post-hysterectomy)
• NOTE – at this time, testosterone and/or chest
binding isn’t believed to increase breast/chest
cancer risk (no clear evidence)
• Person has undergone breast/chest
feminizing surgery
• Regular breast/chest screening recommended if
> 5 years of feminizing hormone therapy
• Person has had top surgery
• Usually, some breast tissue still remains after top
surgery. Discuss with healthcare provider how to
best monitor/screen.
breast cancer screening risks
false positive
overdectection: tx for cnacer that would not have been life threatening if untreated
missed breast cancer
anxiety
low doses of radiation
Breast Cancer Clinical Presentation
(Signs and Symptoms)
• Can be asymptomatic (identified through screening mammography) mostly
• Lump in breast or armpit
• Painless, palpable lump is most common
• Less common:
• Inverted nipple (when it isn’t usually)
• Crusting, bleeding or a rash on nipple
• Nipple discharge
• Dimpling or thickening of the skin in one area of a breast
• Redness/Warmth - Inflammatory breast cancer
• Signs/symptoms of metastatic disease:
• Varies depending on sites
• Bone pain, abdominal pain, mental status changes
• VM is a 48 year old pre-menopausal female who visits your pharmacy
to pick up her refill prescription of Ramipril. She informs you that her
mother was recently diagnosed with breast cancer. She further
explains that she is worried that she may also be at risk of developing
breast cancer and is scared. She asks you what she should do to
minimize her risk and if she should get a mammogram.
• How should you advise VM for minimizing her risk?
• Do you recommend that VM get a mammogram?
Breast awareness
Screening every 2 years
Limit alcohol
Active lifestyle
Healthy weight
Probably wants to start early
• Breast cancer is heterogonous
• Important to characterize the disease as well as possible to inform treatment plan
• Many characteristics to consider including “Prognostic factors/biomarkers” and
“Predictive factors/biomarkers”
• Stage
• Tumour Size (T)
• Size of tumour in cm
• Nodes (N)
• Small bean shaped organs that act as
filters along the lymph fluid channels
• Refers to the number and location of
lymph nodes that have cancer cells
present (“positive” lymph nodes)
• Metastasis (spread to other organs)
Pathology/Biology
• Subtype (cell of origin)
• Grade
• Lymphovascular Invasion
• Ki67
• Predictive Biomarkers
• Hormone Receptors
• HER2 status
• Genetics/Genomics
• Oncotype Dx
• Prosigna
Subtypes
• “In Situ” vs “Invasive”
• In situ:
• Malignant transformation has occurred but basement membrane is intact
• Localized to the one place where the cells formed
• “Stage 0”
• If left untreated (surgery +/- radiation), up to 50% of DCIS will progress to an invasive
disease
• “DCIS” (ductal carcinoma in situ)
• Ductal Carcinoma (75% of all breast cancers)
• Prognosis is poorer than most other types
• Lobular Carcinoma (10% of breast cancers)
Staging - simplified
• Stage 0 – “in situ”
• Stage I
• <2cm AND no spread to lymph nodes
• Stage II
• 2-5cm OR <2cm and spread to lymph
nodes
• Stage III
• >5cm OR lots of lymph node involvement
• Stage IV
• Metastases present in other areas of
body (eg. liver or bone)
ofcancer/breast-cancer#Diagnosis–&–staging
NOTE – Staging recently updated to include grade and biomarker
status. What you see here, is a very simplified version.
Lymphovascular Invasion
• Vascular or lymphatic system
invasion
• Occurs when breast cancer cells
have spread into the blood vessels
or lymph channels
• Increases risk of cancer travelling
to new sites (increased risk of
metastasis)
• DIFFERENT than lymph node
involvement
what is Grade
The grade is a score that
indicates aggressiveness
• Considers cell differentiation
and growth rate.
• Typically higher grade the
more aggressive (and worse
prognosis)
• Typically higher grade may be
more sensitive to
chemotherapy
grade 1,2,3 difference
Grade 1
• Low grade
• Well differentiated, growing in slow,
well-organized patterns
Grade 2
• Intermediate or Moderate Grade
• Moderately differentiated and are
growing more rapidly
Grade 3
• High grade
• Poorly differentiated and dividing
quickly
what is Ki67
• A marker of proliferation
• Expressed as a percentage of the total
cells examined which are proliferating
• Useful when deciding whether or not
a patient may benefit from
chemotherapy
• Cutoff for high versus low remains
controversial and different pathology
labs can have different cut offs
• Low is typically less than 10%
• High is typically over 20%
• 10-20% borderline
low
• Low Ki67 = low proliferation
• Less likely to respond to
chemotherapy
• High Ki67 = high proliferation
• More likely to respond to
chemotherapy
More worrisome cancer if it’s getting big fast
• Hormone receptors are
transcription factors that activate
signal transduction upon ligand
(hormone) binding.
• In other words they are proteins on
breast cells that respond to hormone
signals with cell growth and
proliferation
• Predictive biomarker for response
to endocrine therapy (hormonal
manipulation)
• Hormone receptor positivity is
associated with a higher response
to endocrine therapy (predictive
biomarker)
• “ER”: estrogen receptor
• “PR”: progesterone receptor
• Breast cancers can be classified
as hormone receptor positive
or negative:
• “ER+PR+”
• “ER-/PR-”
• HER2/neu gene is an oncogene
that encodes for the HER2 protein
• HER2 protein:
• normally expressed at low levels in
normal breast epithelial tissue
• overexpression occurs in about 20-
30% of breast cancers
• Overexpression leads to increase is
cell growth signaling
• Overexpression is associated with
increased tumor aggressiveness
• HER2 positivity is a predictive
biomarker for efficacy of HER2
targeted therapies (can target HER2)
Breast cancer can be classified as
HER2 positive or negative (HER2+
or HER2-)
Classification: Predictive Biomarkers
hormone receptor positive?
HER2 receptor positive?
YES NO ER/PR+ HER2- 70%
YES YES ER/PR+ HER2+ 12%
NO NO ER/PR- HER2-
(“triple negative”) 12% –> cannot use any of the drugs
NO YES ER/PR- HER2+ 5%
Genomic Tests
• Provinces may specify which genomic tests are funded and what
criteria patients must meet to obtain the test
• OncotypeDx®
• Assigns a recurrence score to predict which patients are most likely to benefit
from chemotherapy (only for early-stage, N0 or N1, HR+, HER2- breast cancer)
• low RS< 18; intermediate 18-30; or high RS≥ 31
Scores for good prognosis
Is there benefit for chemo?
• Prosigna™ (PAM50)
• Classification of tumors into 4 intrinsic subtypes based on the expression
measures of 50 genes (only for certain types of breast cancer)
If pharmacotherapy is indicated, and the pathology report says
that the breast cancer cells can be characterized as……
• High grade and high Ki-67?
• HER2/neu positive?
• Hormone receptor positive?
• Triple negative (ER negative, PR negative, HER2/neu negative)?
• High grade, HER2/neu positive, Hormone receptor positive?
What type of pharmacotherapy do you think would be indicated?
REMEMBER – predictive biomarkers
Chemo good option
HER2 receptor therapy
Block estrogen
Triple negative cannot use HER2 or block hormone
If everything, give it all
see slidie 30 for treatment options table
ok
Surgery (Stage I-III)
what is lumpectomy, simple, modified, radical mastectomy
Lumpectomy:
Removes the breast tumor without removal of the remaining
surrounding breast tissue
• Simple (or total) mastectomy:
Removes the entire breast without any underlying muscle removal
• Modified radical mastectomy:
Removes the entire breast and includes axillary lymph node
dissection
• Radical mastectomy:
Removes the entire breast tissue along with some of the muscles of
chest and more extensive axillary node dissection
Sentinel Lymph Node Biopsy
Sentinel nodes = the hypothetical first lymph nodes reached by metastasizing cancer cells from a tumor
• Procedure involves injecting radioactive material into the breast and tracing lymphatic drainage to the first lymph node
• If the sentinel nodes are free of cancer, then cancer is unlikely to have spread, and removing additional lymph nodes is unnecessary
N0 no lymph nodes
Lymphedema
• Build up of lymph fluid when lymph node dissection occurs
• Interruption of axillary lymph
drainage from arm
• Caused by axillary dissection or
radiation (or both)
• Approximately 12% of patients;
usually occurs within 4 years of
treatment; can be permanent
• Management: physiotherapy after
surgery, compression, exercises,
massage
Radiation Therapy in Stage I-III Breast Cancer
• In stage I-III breast cancer, considered in the following:
• patients with breast conserving surgery (BCS)
• Lumpectomy or partial/segmental mastectomy
• Patients with close or positive margins
• Patients with high risk features
• Examples: large tumour size, high grade, LVI, younger age
• Rationale in early breast cancer - reduce risk of recurrence
• Sequencing:
• If patient is going to receive adjuvant radiation, then usually AFTER chemotherapy (Too toxic to do it together in this scenario)
• If patient is not going to receive adjuvant chemotherapy, then after post-op healing
is complete.
• Radiation can be concurrent with trastuzumab (HER2 targeted therapy) or endocrine therapy
Radiation in Stage IV Breast Cancer
• Treat metastatic site
• Examples: Brain, Bone
• Palliative Intent
• Improve quality of life (reduce pain at metastatic site)
• Control disease
