CME

Overview of
breast cancer
Elyse J. Watkins, DHSc, PA-C, DFAAPA

ABSTRACT
Each year, more than 250,000 women in the United States
Downloaded from http://journals.lww.com/jaapa by BhDMf5ePHKbH4TTImqenVC/lUCNaSj7M2Ro9VyvswB/aRp8XzEjZJBVgdPrsunBNuHQ88IZI75s= on 12/08/2019

are diagnosed with invasive breast cancer. Although overall

mortality for breast cancer patients has declined, it is still the
second most common cause of cancer death in women. This
article provides an overview of nonmetastatic breast cancer
in women, including general features, diagnostic consider-
ations, and treatments for the most common breast cancer
subtypes.
Keywords: nonmetastatic breast cancer, breast imaging,
DCIS, triple negative, invasive ductal carcinoma, hormone
receptor

Learning objectives
© SEBAST
BASTIAN
IAN KAU
AULITZKI / SHUT
HUTTERS
TER
RSTOC
TOC
OCK
CK
Identify risk factors for development of breast cancer.
Understand the classifications and subtypes of breast
cancer.
PATHOPHYSIOLOGY, RISK FACTORS, AND HISTOLOGY
The pathophysiology of breast cancer is multidimensional
Describe breast cancer treatment options.
and still poorly understood, but certain risk factors are
known. Advancing age and female sex are the most com-
mon risk factors. Genetic mutations, specifically BRCA

C
linicians who work in settings other than oncology
should have an understanding of breast cancer to
help care for women who are at risk, undergoing
a workup for an abnormal mammogram and/or a pal-
pable breast mass, or being treated for breast cancer.
Breast cancer incidence is increasing in almost all eth-
nicities in the United States, and estrogen-positive breast
cancer incidence is increasing across all ethnicities.1 This
cancer is the leading nondermatologic malignancy and
the second most common cause of cancer death among
women in the United States.1 Although overall death rates
from breast cancer have continued to decrease since 1989,
the death rate among non-Hispanic black women remains
disproportionately high.1,2
Up to 80% of invasive breast cancers are infiltrating
ductal carcinomas (IDC). Invasive lobular carcinoma is
the second most common type. Of the noninvasive in situ
carcinomas, more than 80% are ductal and about 10%
are lobular.2
1 and 2, account for about 10% of breast cancers.2 Other
known risk factors include a history of ductal carcinoma
in situ, high body mass index (BMI), first birth at age
greater than 30 years or nulliparity, early menarche
(before age 13 years), family history of breast or ovarian
cancer, late menopause, and postmenopausal hormone
therapy use. Among women who use postmenopausal
hormone therapy, white women and women with a
Elyse J. Watkins is an associate professor in the School of PA Medicine
at the University of Lynchburg in Lynchburg, Va., a lecturer in the PA
program at Florida State University in Tallahassee, Fla., and practices
clinically at Wake Baptist Health in Winston-Salem, N.C. The author has
disclosed no potential conflicts of interest, financial or otherwise.
Acknowledgment: The author would like to thank James R. Sancrant,
DO, of Triad Radiology Associates in Winston-Salem, N.C., for his assis-
tance with this manuscript.
DOI:10.1097/01.JAA.0000580524.95733.3d
Copyright © 2019 American Academy of PAs

JAAPA Journal of the American Academy of PAs www.JAAPA.com 13

Copyright © 2019 American Academy of Physician Assistants

CME
Key points
Although breast cancer mortality is decreasing, incidence
remains high. Clinicians must be aware of the most
common issues and recommendations for breast cancer
diagnostics and treatments.
Not all breast cancer is alike, and treatment
recommendations depend on subtype and other biologic
and immunohistologic markers.
Because estrogen-positive breast cancer is the most
common breast cancer, and more women are surviving
their initial diagnosis, clinicians should be aware of the
common survivorship issues women face.
normal BMI and dense breasts are at greatest risk.3
Women with a history of previous chest radiation also
are at an increased risk.
The four breast cancer subtypes (Table 1) are associ-
ated with specific histologies and prognoses. Breast
cancer also is classified by its anatomical origin, either
lobular or ductal, and its hormone receptivity and human
epidermal growth factor receptor 2 (HER-2) expression.
Hormone receptivity refers to the presence or absence
of estrogen and progesterone receptor expression in
the malignancy. Hormone receptor positive breast
cancer, particularly when nonmetastatic, is amenable
to hormone-blocking therapy. HER-2 positive malig-
nancies are generally responsive to HER-2 directed
monoclonal antibodies. Hormone receptor positive,
HER-2 negative is the most common expression status
of breast cancer.
Triple-negative breast cancer refers to malignancies
that do not express hormone receptivity or HER-2. About
12% of women with breast cancer will have triple-nega-
tive disease.4 Triple-negative disease is more common
among non-Hispanic black women, independent of age,
but tends to be diagnosed at earlier ages than other sub-
types.4 Women with triple-negative disease are also more
likely to be diagnosed at a later stage (stage III or IV). In
addition, triple-negative basal subtype breast cancers tend
to be of higher grade and thus more aggressive malignan-
cies than hormone receptor positive HER-2 negative
disease.
The proliferation biomarker Ki-67 was recently used
to help stratify risk of recurrence in breast cancer. It is no
longer recommended, but other immunohistologic bio-
markers are being discovered and may help to further
stratify recurrence risk.
BREAST CANCER SUBTYPES
Ductal carcinoma in situ (DCIS) is a heterogeneous cat-
egory of noninvasive, noninfiltrating malignancies that
are localized inside the mammary ducts. (Sometimes IDC
also will have mammographic or histologic evidence of
DCIS.2) DCIS is further subclassified depending upon its
14 www.JAAPA.com
Copyright © 2019 American Academy of Physician Assistants
morphology, location, and cytological characteristics.
Lobular carcinoma in situ is less common than DCIS but
tends to occur bilaterally. Both DCIS and LCIS are usually
hormone receptor positive and HER-2 negative.
IDC is the most common type of breast cancer. About
70% of women with IDC will be hormone receptor
positive and HER-2 negative.4
Infiltrating lobular carcinomas (ILCs) are more common
among postmenopausal women and have an increased
risk of bilateral incidence. They are almost always estro-
gen and progesterone receptor positive.2
Medullary breast cancer is more common in younger
women who carry a BRCA 1 mutation.5 Inflammatory
breast cancer is less common but more aggressive, and
carries a worse prognosis than other breast cancers.
Mammary Paget disease is an adenocarcinoma affecting
the nipple and areola. Tubular, papillary, and mucinous
breast cancers and Phylloides tumors are less common
cancers.5
CLINICAL ASSESSMENT AND DIFFERENTIAL
A palpable breast mass is evident in about 30% of
women with breast cancer.2,6 Visible signs associated
with breast cancer include dimpling, an orange-peel
appearance (peau d’orange), erythema, edema, blister-
ing, excoriations, sanguineous nipple discharge, and
nipple retraction. Skin changes such as peau d’orange
and blistering are strongly associated with inflammatory
Breast cancer requires
a multidisciplinary approach
to diagnose and manage.
breast cancer and Paget disease of the breast. Sanguin-
eous nipple discharge is associated with papillary breast
neoplasia. Ulcerations can be seen in advanced disease.
Remember to rule out malignancy in patients being
treated for mastitis or a breast abscess that is not
improving clinically.
The differential diagnosis of a palpable breast mass in
a woman includes benign conditions such as fibroade-
noma, breast cyst, intraductal papilloma, and fibrocystic
changes. Once a mass has been palpated, the next steps
are to refer the patient for a diagnostic mammogram and
ultrasound.
DIAGNOSIS
Mammography and ultrasonography are used as initial
imaging modalities. MRI may be used in specific cir-
cumstances, such as in patients with dense breasts, those
with a history of breast cancer, those who are being
Volume 32 • Number 10 • October 2019

evaluated for contralateral disease, and those at high
risk for breast cancer.7 MRI also can be used in the
presurgical planning of biopsy-proven breast cancer or
in the evaluation of patients with dense breasts, con-
tralateral disease, or a history of breast surgery or
radiation. MRI can more accurately identify skin changes
common in inflammatory breast cancer, such as skin
invasion.
Common imaging findings in invasive, infiltrating breast
cancer include an irregularly shaped mass, spiculation,
pleomorphic microcalcifications, anatomical distortion,
axillary lymphadenopathy, and posterior acoustic shad-
owing. The American College of Radiology uses the Breast
Imaging and Reporting Data System (BI-RADS) to cat-
egorize radiographic findings.8
Disease is confirmed by tissue biopsy; samples can be
obtained through percutaneous ultrasound-guided core
needle biopsy, excisional biopsy, stereotactic biopsy, or
MRI-guided biopsy. The preferred method for most
patients is ultrasound-guided large-bore core needle biopsy
with or without a vacuum-assisted device.
Tissue biopsy results will contain information about:
• Tumor grade, which is based on cell differentiation.
Low-grade tumors (grade 1) are well differentiated, and
high-grade (grade 4) tumors are undifferentiated.
• Immunohistology, based on the tumor’s hormone recep-
tivity and HER-2 expression.
• Oncotype DX Breast Recurrence Score, which provides
an estimate of the potential utility of neoadjuvant che-
TABLE 1. Breast cancer subtypes
Subtype Immunohistochemistry
• Estrogen receptor positive
Luminal A • Progesterone receptor positive
• HER-2 negative
• Estrogen receptor positive
Luminal B • Progesterone receptor positive
• HER-2 positive or negative
• Estrogen receptor negative
HER-2 positive • Progesterone receptor negative
• HER-2 positive
• Estrogen receptor negative
Triple negative
• Progesterone receptor negative
(basal)
• HER-2 negative
Reprinted with permission of Springer Publishing Co. LLC from Watkins E, The Physician Assistant Student’s Guide to the Clinical Year: OB-GYN.
JAAPA Journal of the American Academy of PAs
Copyright © 2019 American Academy of Physician Assistants
Overview of breast cancer
motherapy and risk of recurrence in patients with early-
stage breast cancer.
Breast cancer is staged using the TNM (tumor, nodes,
metastasis) classification system. Most women with a
biopsy-proven malignancy should undergo genetic testing
for BRCA 1 and 2 mutations (Table 2).9
Cowden syndrome and Li-Fraumeni syndrome also are
associated with an increased risk of breast cancer. Patients
with a family history of cancer of the breast, ovary, pan-
creas, prostate, colon, thyroid, or endometrium should
undergo more extensive genetic testing.10
MANAGEMENT
Treatment of breast cancer, including surgery, depends on
the size of the lesion, hormone receptivity and histologic
markers, presence or absence of metastatic or contralateral
disease, patient age, and patient preference.
Surgical options include lumpectomy, mastectomy, and
bilateral mastectomy. Breast-conserving surgery (lumpec-
tomy) is the preferred intervention for most patients with
unilateral disease, but many patients still opt for mastectomy.
Sentinel lymph node biopsy is preferred over wide lymph
node dissections if the patient has no radiographic or
clinical evidence of axillary lymph node involvement. In
patients with evidence of lymph node involvement, expert
consensus remains mixed as to whether axillary node
dissection has clinical benefit.11
Chemotherapeutic options depend on multiple vari-
ables, including hormone reception status, HER-2 status,
Prognosis Notes
• The most common subtype
• Usually lower-grade tumors
• Usually diagnosed at early stages
Good
• Responsive to hormone therapies such as SERMs and
aromatase inhibitors
• Lowest rate of recurrence
• Tend to be of higher grade
Fair
• Tend to recur more frequently than luminal A
• Some tumors may be amenable to anti-HER-2 monoclonal
antibodies
Poor • Not all tumors respond to anti-HER-2 monoclonal antibodies
• Resistance develops in most patients to anti-HER-2
monoclonal antibodies (particularly trastuzumab)
• More common in black women
• Age at diagnosis usually younger than other subtypes
Poor
• Not amenable to hormone therapy or HER-2 therapy
• Tends to be aggressive with high rates of recurrence
www.JAAPA.com 15
CME
presence or absence of metastatic disease, and Oncotype
DX recurrence score. Locally advanced disease and triple-
negative breast cancer usually are treated with presurgi-
cal neoadjuvant chemotherapy. Chemotherapeutic agents
include doxorubicin, cyclophosphamide, and paclitaxel.
Doxorubicin can cause significant nausea, vomiting,
diarrhea, and fatigue. Some women will experience a
discoloration of their nails. A reddish discoloration of
urine, tears, and sweat also can occur. Heart failure has
been documented in women receiving doxorubicin, so
carefully assess patients’ cardiac function. Cyclophos-
phamide can cause neutropenia, alopecia, and significant
nausea and vomiting. Paclitaxel can cause neutropenia,
alopecia, arthralgias, myalgias, peripheral neuropathy,
and mucositis. A discussion of chemotherapeutic options
for recurrent or metastatic breast cancer is beyond the
scope of this article.
Adjuvant chemotherapy is administered after surgery.
Modalities include endocrine blockers, anthracycline- and
taxane-based chemotherapy, and monoclonal antibodies,
depending upon the histology, HER-2 status, and hormone
receptor status of the malignancy.10
Aromatase inhibitors and selective estrogen receptor
modulators (SERMs) can be used for nonmetastatic
estrogen and progesterone receptor positive breast cancer.12
HER-2 positive breast cancer can be responsive to HER-2
blockers such as pertuzumab and trastuzumab. Neoad-
juvant and adjuvant anthracycline-based chemotherapy,
in addition to HER-2 blocking monoclonal antibodies,
has shown clinical superiority.10 Monitor left ventricular
ejection fraction before and during treatment in patients
who are treated with trastuzumab. Primary resistance to
trastuzumab is present in more than 30% of patients, and
secondary resistance occurs in more than 70% of patients.13
SERMs are used in premenopausal patients. Current
recommendations for hormone-positive breast cancer are
to use a SERM for 5 years followed by an aromatase
inhibitor for 5 years. High-risk patients (those under age
35 years with positive nodes, high-grade, or large tumors)
who are hormone receptor positive and HER-2 negative
may benefit from using the aromatase inhibitor exemestane
plus chemical ovarian suppression with a gonadotropic-
releasing hormone agonist, oophorectomy, or ovarian
radiation.14 Tamoxifen is the most commonly used SERM.
TABLE 2. Criteria for BRCA 1 and 2 screening9
• Breast malignancy diagnosed at age 50 years or younger
• Bilateral breast malignancy
• Personal or family history of breast or ovarian cancer
• Multiple breast malignancies in a patient’s family
• Male breast cancer in a patient’s family
• Ashkenazi Jewish heritage
16 www.JAAPA.com
Copyright © 2019 American Academy of Physician Assistants
Tamoxifen use has some association with endometrial
hyperplasia and carcinoma, so patients are advised to
report any new abnormal uterine bleeding to their gyne-
cologist. Avoid coprescribing paroxetine, fluoxetine,
bupropion, and duloxetine, because these medications are
strong inhibitors of CYP2D6 and may lower tamoxifen’s
effectiveness. Escitalopram, citalopram, sertraline, and
desvenlafaxine are moderate inhibitors of CYP2D6. Ven-
lafaxine seems to have a negligible effect on CYP2D6.15
Aromatase inhibitors are used in women with natural
and surgically induced menopause. The National Com-
prehensive Cancer Network provides guidance in diag-
nosing menopause in patients with breast cancer. Consider
a woman postmenopausal if she is:
• age 60 years or older
• has had an oophorectomy
• under age 60 years and has been amenorrheic for at
least 12 months without any exogenous medications that
could alter ovarian function
• under age 60 years and taking a SERM, but has serum
estradiol and/or follicle-stimulating hormone levels that
are consistent with menopause.10
Women who take aromatase inhibitors experience accel-
erated bone loss, so regular monitoring of bone density is
recommended. Consider prescribing bisphosphonates in
postmenopausal women with hormone receptor positive
breast cancer to help prevent further bone loss from aro-
matase inhibitor therapy. Aromatase inhibitors can cause
significant joint pain. Patient education and support are
necessary to help ensure adherence. Treatment of aroma-
tase-induced arthralgia includes NSAIDs and acetamino-
phen. Patients may find relief from physical therapy,
acupuncture, exercise, and other complementary therapies.
Triple-negative basal subtype breast cancer is managed
with a combination of doxorubicin, cyclophosphamide,
and paclitaxel. Clinical trials with immunotherapies and
other targeted therapies are underway. Because triple-
negative breast cancer does not have endocrine receptiv-
ity, endocrine therapy is not indicated.
Radiation therapy is almost always used, either before
surgery or more commonly after it. Whole-breast and tar-
geted nodal radiation have been considered the gold standard
treatment. Women typically receive radiation therapy five
times a week for 4 to 7 weeks. A “boost” of lower radiation
may be considered in women at high risk of recurrence.
Accelerated partial breast irradiation may be considered in
women over age 50 years who are node-negative, hormone
receptor positive, and BRCA-negative.10 Women who
undergo breast-conserving surgery receive postsurgical
radiation of the breast and axilla. In women with positive
lymph nodes and tumors greater than 5 cm, radiation may
be used on the axilla, supraclavicular areas, and sternum.10
Presurgical radiation therapy often is used for tumors
that have been staged at T2 or higher, using specific criteria
to guide radiation decisions. Recent data suggest that
Volume 32 • Number 10 • October 2019

women age 65 years and older with hormone receptor
positive, node-negative disease with a primary tumor less
than 3 cm may have the option of foregoing radiation.16
Patients undergoing radiation are advised to avoid the
use of deodorants, antiperspirants, and underwire bras.
In addition, patients should avoid the use of topical
creams, lotions, and ointments before their treatments
because thicker applications could affect the radiation
dose received.17 They should not use heavily perfumed
lotions and creams on the breast, and use only specific
topical products (such as aloe vera and hydrocortisone)
on skin burns that occur during radiation therapy. Other
adverse reactions common to patients undergoing radia-
tion include fatigue, pain, and breast discoloration. Women
with large breasts are also at risk of developing a candi-
dal dermatitis under the breast. Prompt treatment with
an appropriate antifungal is essential.
BREAST CANCER SCREENING
The US Preventive Services Taskforce (USPSTF) recom-
mends screening mammography in women ages 50 to
74 years.18 Women ages 40 to 49 years should have a
screening regimen based on the best-available evidence,
including the patient’s risk factors, through shared
decision-making.18 Annual mammography is not recom-
mended for average-risk women in any age group, and
the benefit of screening in women over age 75 years has
not been established.18 However, the American College
of Obstetricians and Gynecologists (ACOG) advocates
for individualized shared decision-making about screen-
ing with each patient, taking into consideration the
patient’s risk factors and values.19 Monthly breast self-
examinations are not explicitly recommended by any
professional organization and clinical breast examination
recommendations vary by professional organization.
ACOG and the National Comprehensive Cancer Network
recommend clinical breast examinations every 1 to 3
years, but the American Cancer Society and the USPSTF
do not recommend clinical breast examinations.19
CONCLUSION
Breast cancer is a multifactorial, heterogeneous disease
that requires clinical acumen and a multidisciplinary
approach to diagnose and manage. Clinicians working in
nononcology settings are likely to encounter patients who
are in the early stages of diagnosis and later stages of
treatment, thus an understanding of the current state of
the evidence will help guide the care of these patients. JAAPA
Earn Category I CME Credit by reading both CME articles in this
issue, reviewing the post-test, then taking the online test at http://
cme.aapa.org. Successful completion is defined as a cumulative
score of at least 70% correct. This material has been reviewed and is
approved for 1 hour of clinical Category I (Preapproved) CME credit
by the AAPA. The term of approval is for 1 year from the publication
date of October 2019.
JAAPA Journal of the American Academy of PAs
Copyright © 2019 American Academy of Physician Assistants
Overview of breast cancer
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www.JAAPA.com 17