i3 Health is pleased to make the Clinician's Resource Guide from this activity available for use as a nonaccredited self-study or teaching resource.

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Clinical Tools and Resources for
Self-Study and Patient Education
TRIPLE-NEGATIVE BREAST CANCER
REFERENCE GUIDE
The clinical tools and resources contained herein are provided as educational adjuncts to the
CME/CE-approved online activity Implementing New Data and Evolving Standards in Metastatic
Triple-Negative Breast Cancer. To access the activity and earn CME/CE credit, visit:
https://www.i3Health.com/tnbc
CONTENTS
I. General Staging of Breast Cancer......................................................................................................2
II. TNM Classifications of Breast Cancer ...............................................................................................4
III. Guidelines for Systemic Adjuvant Treatment: Triple-Negative Breast Cancer.................................6
IV. Chemotherapy for Recurrent or Metastatic Triple-Negative Breast Cancer ....................................7
V. Targeted Therapy and Immunotherapy for Metastatic Triple-Negative Breast Cancer....................8
VI. Patient Education: Side Effects of Treatment for Triple-Negative Breast Cancer..........................10

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I. GENERAL STAGING OF BREAST CANCER
Stage Description
Stage 0
• Carcinoma in situ (DCIS)
• Non-invasive: the cancer cells are still within a duct and have not invaded the surrounding fatty
breast tissue
• No spread to lymph nodes or distant sites
Stage IA
• Tumor is ≤2 cm across
• No spread to lymph nodes or distant sites
Stage IB
• Tumor is ≤2 cm across (or is not found)
• Micrometastases in 1-3 axillary lymph nodes (the cancer in the lymph nodes is >0.2 mm across
and/or >200 cells but ≤2 mm across)
• No spread to distant sites
Stage IIA
One of the following applies, and the cancer has not spread to distant sites:
• Tumor is ≤2 cm across (or is not found); spread to 1-3 axillary lymph nodes, with the cancer in the
lymph nodes >2 mm across
• Tumor is ≤2 cm across (or is not found); tiny amounts of cancer are found in internal mammary
lymph nodes on sentinel lymph node biopsy
• Tumor is ≤2 cm across (or is not found); spread to 1-3 lymph nodes under the arm and to internal
mammary lymph nodes (found on sentinel lymph node biopsy)
• Tumor is >2 cm across and <5 cm; no spread to lymph nodes
Stage IIB
One of the following applies, and the cancer has not spread to distant sites:
• Tumor is >2 cm and <5 cm across; spread to 1-3 axillary lymph nodes and/or tiny amounts of
cancer found in internal mammary lymph nodes on sentinel lymph node biopsy
• Tumor is >5 cm across but does not grow into the chest wall or skin; no spread to lymph nodes
Stage IIIA
One of the following applies, and the cancer has not spread to distant sites:
• Tumor is ≤5 cm across (or cannot be found); spread to 4-9 axillary lymph nodes
• Tumor is >5 cm across but does not grow into the chest wall or skin; spread to 1-9 axillary nodes
or to internal mammary nodes
Stage IIIB
Tumor has grown into the chest wall or skin but has not spread to distant sites. One of the following
applies:
• No spread to lymph nodes
• Spread to 1-3 axillary lymph nodes and/or tiny amounts of cancer found in internal mammary
lymph nodes on sentinel lymph node biopsy
• Spread to 4-9 axillary lymph nodes, or tumor has enlarged the internal mammary lymph nodes

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Stage
(cont.)
Description (cont.)
Stage IIIC
The tumor is any size (or cannot be found) with no spread to distant sites. One of the following
applies:
• Spread to >10 axillary lymph nodes
• Spread to the lymph nodes under the clavicle
• Spread to the lymph nodes above the clavicle
• Involvement of axillary lymph nodes
• Spread to ≥4 axillary lymph nodes, with tiny amounts of cancer found in internal mammary
lymph nodes on sentinel lymph node biopsy
Stage IV
• Tumor can be of any size
• May or may not have spread to nearby lymph nodes
• Spread to distant organs or to lymph nodes far from the breast
• Most common sites of spread: bone, liver, brain, or lung
National Cancer Institute (2019). Triple-negative breast cancer staging. Available at: https://www.pennmedicine.org/cancer/types-of-
cancer/breast-cancer/types-of-breast-cancer/triplenegative-breast-cancer/triplenegative-breast-cancer-diagnosis/triplenegative-
breast-cancer-staging

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II. TNM CLASSIFICATIONS OF BREAST CANCER
Tumor
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis (DCIS) Ductal carcinoma in situ
Tis (Paget)
Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS) in
the underlying breast parenchyma (tissue)
T1 Tumor £20 mm in greatest dimension
T1mi Tumor £1 mm in greatest dimension
T1a Tumor >1 mm but £5 mm in greatest dimension
T1b Tumor >5 mm but £10 mm in greatest dimension
T1c Tumor >10 mm but £20 mm in greatest dimension
T2 Tumor >20 mm but £50 mm in greatest dimension
T3 Tumor >50 mm in greatest dimension
T4 Tumor of any size with direct extension to the chest wall and/or skin (ulceration or macroscopic nodules)
T4a Extension to the chest wall
T4b
Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema of the skin that does not meet
the criteria for inflammatory carcinoma
T4c Both T4a and T4b are present
T4d Inflammatory carcinoma
Node
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis identified; alternately, isolated tumor cells (ITCs) only
pN0(i+) ITCs only: malignant cell clusters ≤0.2 mm) in regional lymph node(s)
pN0(mol+)
Positive molecular findings by reverse transcriptase polymerase chain reaction (RT-PCR); no ITCs
detected
pN1
Micrometastases, metastases in 1-3 axillary (armpit) lymph nodes, and/or clinically negative internal
mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy
pN1mi Micrometastases (approximately 200 cells, >0.2 mm and <2.0 mm in size)
pN1a Metastases in 1-3 axillary lymph nodes, with at least one metastasis >2.0 mm
pN1b Metastases in ipsilateral internal mammary sentinel nodes, excluding ITCs
pN1c pN1a and pN1b combined

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Node (cont.)
pN2
Metastases in 4-9 axillary lymph nodes or positive ipsilateral internal mammary lymph nodes by
imaging in the absence of axillary lymph node metastases
pN2a Metastases in 4-9 axillary lymph nodes (at least one tumor deposit >2.0 mm)
pN2b
Metastases in clinically detected internal mammary lymph nodes with or without microscopic
confirmation; pathologically negative axillary nodes
pN3
Metastases that satisfy any of the following conditions:
• Present in ≥10 axillary lymph nodes
• Present in infraclavicular (below the clavicle, or collar bone) (Level III axillary) lymph nodes
• Positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or
more positive Level I or II axillary lymph nodes
• Present in >3 axillary lymph nodes, as well as micrometastases or macrometastases by
sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes
• Present in ipsilateral supraclavicular lymph nodes (lymph nodes above the clavicle)
pN3a Metastases in ≥10 axillary lymph nodes (at least one tumor deposit >2.0 mm)
pN3b
Either pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging) or
pN2a in the presence of pN1b
pN3c Metastases in ipsilateral supraclavicular lymph nodes
Metastasis
M0 No clinical or radiographic evidence of distant metastases
cM0(i+)
No clinical or radiographic evidence of distant metastases in the presence of tumor cells; alternately,
deposits ≤0.2 mm detected microscopically or by molecular techniques in circulating blood, bone
marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastases
cM1 Distant metastases detected by clinical and radiographic means
pM1
Any histologically proven metastases in distant organs, or if in non-regional nodes, metastases >0.2
mm
Amin MB, Edge S, Green F, et al (2017). AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer.

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III. GUIDELINES FOR SYSTEMIC ADJUVANT TREATMENT: TRIPLE-
NEGATIVE BREAST CANCER
National Comprehensive Cancer Network (2019). Clinical Practice Guidelines in Oncology: breast cancer. Version 1.2019. Available at:
http://www.nccn.org

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IV. CHEMOTHERAPY FOR RECURRENT OR METASTATIC TRIPLE-NEGATIVE
BREAST CANCER
Chemotherapy Options
Preferred
single agents
• Doxorubicin (Adriamycin®, Rubex®)
• Paclitaxel (Abraxane®, Taxol®)
• Gemcitabine (Gemzar®)
• Eribulin (Halaven®)
• Liposomal doxorubicin (Doxil®)
• Capecitabine (Xeloda®)
• Vinorelbine (Navelbine®)
Other single
agents
• Cyclophosphamide (Cytoxan®, Neosar®)
• Docetaxel (Taxotere®)
• Cisplatin (Platinol®)
• Ixabepilone (Ixempra®)
• Carboplatin (Paraplatin®)
• Albumin-bound paclitaxel (Abraxane®)
• Epirubicin (Ellence®)
Combination
regimens
• Doxorubicin/cyclophosphamide
• Epirubicin/cyclophosphamide
• Cyclophosphamide/methotrexate/fluoroucacil (Trexall®, Rasuvo®, Otrexup®)/(Efudex®,
Fluoroplex®, Carac®)
• Docetaxel/capecitabine
• Gemcitabine/paclitaxel
• Gemcitabine/carboplatin
• Paclitaxel/bevacizumab (Avastin®)
National Comprehensive Cancer Network (2019). Clinical Practice Guidelines in Oncology: breast cancer. Version 1.2019. Available at:
http://www.nccn.org

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V. TARGETED THERAPY AND IMMUNOTHERAPY FOR METASTATIC TRIPLE-
NEGATIVE BREAST CANCER
Class Agents Adverse Events
PARP Inhibitors
• The poly ADP-ribose polymerase
(PARP) enzyme fixes DNA damage
in both healthy and cancer cells
• Research has shown that
medicines that interfere with or
inhibit the PARP enzyme make it
harder for cancer cells with a
BRCA1 or BRCA2 mutation to fix
DNA damage
• This makes it harder for the cancer
cells to survive
Olaparib
(Lynparza®)
Talazoparib
(Talzenna®)
Bone marrow problems: myelodysplastic syndrome (MDS) or
acute myeloid leukemia (AML). Symptoms:
• Weakness
• Weight loss
• Fever
• Frequent infections
• Blood in urine or stool
• Shortness of breath
• Feeling very tired
• Bruising or bleeding more easily
Common side effects:
• Nausea or vomiting
• Low red or white blood cell count
• Tiredness or weakness
• Sore throat or runny nose
• Diarrhea
• Joint, muscle, and back pain
• Headache
• Constipation
• Changes in the way food tastes
• Loss of appetite
• Mouth sores
• Respiratory infections
• Changes in kidney function blood test
• Indigestion or heartburn
• Low platelet count
• Hair loss
Breastcancer.org (2018). Triple-negative breast cancer. Available at: https://www.breastcancer.org/symptoms/diagnosis/trip_neg
Lynparza® (olaparib) prescribing information (2018). AstraZeneca. Available at: https://www.lynparza.com/breast-cancer/breast-
cancer-treatment-side-effects.html
Talzenna® (talazoparib) prescribing information (2018). Pfizer. Available at: https://www.talzenna.com

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Class (cont.)
Agents
(cont.)
Adverse Events (cont.)
Monoclonal Antibodies
• Molecules produced in
laboratories to substitute
antibodies that can
restore, enhance or mimic
the immune system’s
attack on cancer cells
• Bind to antigens that are
usually more present on
cancer cell surfaces than
healthy cell surfaces
Atezolizumab
(Tecentriq®)
Severe side effects:
• Lung problems (pneumonitis): new or worsening cough,
shortness of breath, and chest pain
• Liver problems (hepatitis): yellowing of skin/whites of eyes,
severe nausea or vomiting, pain on right side of stomach,
drowsiness, dark urine (tea-colored), easy bleeding or bruising,
reduced hunger
• Intestinal problems (colitis): diarrhea or increase in bowel
movements; blood or mucus in stools or dark, tarry, sticky
stools; severe abdominal pain or tenderness
• Hormone gland problems (especially the thyroid, adrenal
glands, pancreas, and pituitary): headaches, extreme
tiredness, weight gain or loss, dizziness or fainting, increased
hunger or thirst, hair loss, changes in mood or behavior (such
as decreased libido, irritability, or forgetfulness), chills,
constipation, deepening of the voice, frequent urination,
nausea or vomiting, abdominal pain
• Problems in other organs: severe muscle weakness, numbness
or tingling in hands or feet, confusion, blurry vision, double
vision, changes in mood or behavior, extreme sensitivity to
light, neck stiffness, eye pain or redness, skin blisters or
peeling, chest pain, irregular heartbeat, shortness of breath,
swelling of ankles
• Severe infections: fever, cough, flu-like symptoms, frequent or
painful urination, back pain
• Severe infusion reactions: chills, shaking, itching or rash,
flushing, shortness of breath or wheezing, swelling of face or
lips, dizziness, fever, feelings of faintness, back or neck pain
Common side effects:
• Fatigue
• Nausea
• Constipation
• Cough
• Shortness of breath
• Decreased appetite
Tecentriq® (atezolizumab) prescribing information (2019). Genentech. Available at: https://www.tecentriq.com

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VI. PATIENT EDUCATION: SIDE EFFECTS OF TREATMENT FOR TRIPLE-
NEGATIVE BREAST CANCER
TNBC Treatment Side Effects
Adverse Event Description Management
Cognitive
dysfunction
(“Chemo
brain”)
A constellation of cognitive symptoms
resulting from chemotherapy:
• Trouble remembering words or
directions
• Difficulty concentrating
• Memory lapses in the middle of
tasks
• Feeling of being in a mental fog
• Use a planner or calendar to keep track of “to do” lists
and events
• Focus on the task at hand (it’s ok not to multitask!)
• Organize your home and work spaces; keep important
items such as keys in a specific place
• Tell your friends and family that you’re having trouble
so they can help you remember important information
• Keep a record of the problems you have and report
them to a healthcare provider
Fatigue
• One of the most common side
effects of cancer and its treatment
• Often described as “paralyzing”
• Comes on suddenly, does not
result from activity or exertion,
and is not relieved by sleep
• May persist throughout treatment
and even for a few months
afterward
• Accept help from others who want to lighten your load
• Engage in regular moderate exercise, especially
walking. This decreases fatigue
• Nap when you can, but limit naps to 30 minutes
• Get 8 hours of sleep per night
• Set a routine for sleeping and waking
• Conserve energy by setting priorities and planning to
do the most important things when you have the most
energy
Hair loss
(alopecia)
• Patient may lose eyebrows,
eyelashes, and other body hair in
addition to the hair on their head
• Radiation therapy may cause loss
of hair in the treated area
• If you choose to have a wig, buy it before treatment
begins to help match it to your own hair. Also consider
turbans, scarves, and hats
• Your health insurance may cover wigs. If so, ask your
doctor to write “cranial prosthesis” on the prescription
rather than “wig”
• Use a mild shampoo and a soft brush or wide-toothed
comb
• Avoid using elastic hair bands, which can cause
breakage
• Sleep on a satin pillowcase
• Ask your doctor if using a cooling cap during
treatment would be appropriate for you

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TNBC Treatment Side Effects (cont.)
Adverse Event Description Management
Lymphedema
• The lymphatic system carries white
blood cells throughout the body to help
fight infections
• Lymph node removal during treatment
can cause a buildup of lymphatic fluid,
resulting in swelling in the area where
the lymph nodes were removed, most
often in an arm or leg
• Lymphedema typically occurs
immediately after surgery or radiation
therapy, but it can also become an issue
months or even years after treatment
ends
• Use a compression garment or tight bandages to
apply pressure to the area
• Elevate the swollen limb to encourage drainage
of the lymphatic system
• Talk to your doctor about manual lymphatic
drainage (MLD), a gentle skin massage that helps
drain lymphatic fluid into the bloodstream,
reducing swelling
• Also ask about complete decongestive therapy
(CDT), which combines manual massage with
skin care, exercise, and compression
Nausea and
vomiting
• Most often caused by chemotherapy
treatments
• Eat smaller, more frequent meals throughout the
day
• Eat at the times of the day when you feel best
• Avoid spicy and fatty foods and avoid foods with
citric acid (such as citrus fruits). Bland foods, such
as bananas and crackers, are easier to digest
• Foods and drinks that include ginger can be
soothing
• Peppermint can relieve nausea
• Drink plenty of fluids
Neuropathy
• Pain or discomfort caused by damage to
the nerves that control movement and
feeling in the arms and legs
• Symptoms: numbness, pain, burning,
tingling, or loss of feeling in the hands
or feet
• If you have these symptoms, keep a
journal of when they happen, what they
are, how long they last, and how intense
they are. Share this information with
your health care team
• Avoid tight-fitting clothes
• Wear comfortable shoes
• Keep your hands and feet warm
• Avoid standing or walking for extended periods
Patient Resource (2019). Triple negative breast cancer. Available at: https://www.patientresource.com/TNBC_Side_Effects.aspx