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29 How toManage Hernias inLimited-Resource Settings
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How toDiagnose andTreat Benign
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andMalignant Diseases
30
oftheBreast inLowandMiddle-Income Countries
SojiF.Oluwole andOlakunleO.Oluwole
Often we look so long at the closed door that we do not see the one that has been opened
for us.
– Helen Keller
Abbreviations
AI Aromatase inhibitor
ALND Axillary lymph node dissection
DCIS Ductal carcinoma in situ
ER Estrogen receptor
FNA Fine needle aspiration
HER Human epithelial growth factor receptor
HR Hormone receptor
LCIS Lobular carcinoma in situ
LMICs Low- and middle-income countries
MRI Magnetic resonance imaging
PR Progesterone receptor
SERM Selective estrogen receptor modulator
S. F. Oluwole (*)
Emeritus Professor of Surgery, Columbia University
College of Physicians & Surgeons,
New York, NY, USA
Harlem Hospital Center, New York, NY, USA
Cancer Control Center of Harlem,
New York, NY, USA
Obafemi Awolowo University, Ile Ife, Nigeria
Old Tappan, NJ, USA
e-mail: so5@columbia.edu
O. O. Oluwole
Old Tappan, NJ, USA
SLNB Sentinel lymph node biopsy
USG Ultra-sonography
Introduction
Breast diseases, both benign and malignant, are
major public health problems encountered in
general surgical practices worldwide, especially
in low- and moderate-income countries
(LMICs). Breast cancer is the most common
female cancer worldwide and second leading
cause of female cancer death in the USA [1].
Increased awareness of the disease in the
wealthy countries and promising new approaches
to screening that include mammography and
magnetic resonance imaging- targeted biopsy
have led to the detection of early- stage breast
cancer in women with non-palpable abnormalities [2]. This has not been true in most LMICs
because of lack of sufcient number and kind of
equipment, and lack of education about the seriousness of the problem. Since the presence of
any breast mass raises the question of cancer, it
is important to understand the statistical relationship between a variety of benign and malignant lesions of the breast.
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
M. A. Hardy, B. R. Hochman (eds.), Global Surgery, https://doi.org/10.1007/978-3-031-28127-3_30
361
362
LHRH = LH-releasing hormone
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S. F. Oluwole and O. O. Oluwole
Despite recent innovative advances in the
detection, treatment, and chemoprevention of
breast cancer, frequently not readily available in
LMICs, surgery remains the cornerstone for most
women diagnosed with this disease [3]. Reported
reduction in breast cancer deaths among women
in the USA and Europe has been attributed to
early disease diagnosis, surgery, and systemic
chemotherapy [4]. The early excision of ductal
carcinoma in situ might also have reduced the
incidence of invasive carcinoma [5]. In LMICs
early diagnosis continues to be difcult, especially in the rural areas.
Anatomy
The details of the anatomy of the female breast
may be found on Google or in most anatomy
books. Of importance is that the breast consists
of 15 to 20 lobes, each has its duct which opens
through a small orice onto the nipple. The areola, nipple, and mouth of the lactiferous ducts are
covered by squamous epithelium. Blood supply
to the breast arises from three main sources,
namely, branches of the axillary artery, perforating branches of the internal mammary artery, and
lateral branches of the posterior intercostal arter-
ies. The venous drainage of the breast follows the
course of the arterial supply. As described by
Haagensen [6], the lymphatic drainage of the
breast comprises 6 main groups of axillary lymph
nodes and the internal mammary lymph node
group. The important nerves encountered during
breast surgery consist of (1) long thoracic nerve
of Bell which innervates the serratus anterior; (2)
the thoracodorsal nerve supplies latissimus dorsi
(its injury causes winged scapula syndrome); and
(3) the other nerves are primarily sensory and are
third and fourth branches of the cervical plexus
and the thoracic intercostal nerves which supply
the skin of the upper part of the breast and the
lower part of the breast, respectively, while
branches of the second intercostal nerve supply
the medial aspect of the upper half of the arm.
Hormonal Regulation oftheBreast
Figure 30.1 illustrates interaction of a number of
hormones that are responsible for the development, function, and maintenance of the female
mammary gland during puberty, pregnancy, and
lactation. Of interest is that manipulation of these
hormones is actively utilized in the treatment of
breast cancer.
Fig. 30.1 Hormones
regulating the breast
Gonadotrophins
(FSH + LH)
Premenopausal
Pituitary gland
LHRH
(hypothalamus)
Pre/post
menopausal
ACTH
ACTH = adrenocorticotrophic hormone;
FSH = follicle-stimulating hormone;
LH = luteinising hormone;
Ovary
Prolactin
Growth hormone
Corticosteroids
Adrenal
glands
Androgens
Progesterone
Estrogens
Progesterones
Estrogens
Peripheral
conversion
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Estrogen and progesterone promote the growth
of some breast cancers, which are called hormonesensitive (or hormone dependent) breast cancers.
Breast cancer cells contain proteins called hormone receptors (estrogen receptors (ERs) and progesterone receptors (PRs)) that become activated
when hormones bind to them. The activated receptors cause changes in the expression of specic
genes, which can stimulate cell growth.
Tumor cells that contain estrogen receptors
are called estrogen receptor positive (ER positive), estrogen sensitive, or estrogen responsive.
Similarly, tumor cells that contain progesterone
receptors are called progesterone receptor positive (PR positive). Breast tumors that contain
estrogen and or progesterone receptors are called
hormone receptor positive (HR positive). Most
ER-positive breast cancers are also PR positive.
Breast cancers that lack ER are called ER negative, and if they lack both ER and PR they may be
called HR negative. Approximately 67% to 80%
of breast cancers in women are ER positive [7].
Additionally, 90% of breast cancers in men are
ER positive and approximately 80% are PR positive [8].
Table 30.1 Relevant history of common breast
problems
Start with risk assessment:
•Age
•Personal history of breast disease
•Family history of breast cancer
•Early menarche and late menopause
•Parity and age at delivery of rst child
•Hormone replacement therapy
•Oral birth control
•Hereditary cancer syndrome, e.g., BRCA
•Obesity
•Radiation exposure
Note that >75% of women with newly diagnosed breast
cancer have no identiable risk factors
retraction/dimpling, nipple retraction, ulceration
or itching, and an axillary mass. Unlike white
women in the USA and in Europe, many women
in LMICs, especially in Africa, present with foul
smelling, fungating, and ulcerated mass [10].
History also includes answers to questions related
to breast diseases like age, reproductive history,
family history of breast disease, previous history
of hormonal replacement therapy, and radiation
to chest wall (Table30.1).
Evaluation oftheBreast
History
The goal of breast evaluation is to determine if a
patient who presents with a breast problem/complaint has normal physiologic breast variations,
clearly dened benign disorder, or possibly
malignant disease. This involves taking a thorough medical history from a patient who may be
frightened because of the fear of having breast
cancer. Careful questioning will reassure the
patient, give her condence, provide important
diagnostic information, and result in a good
doctor- patient relationship.
The history usually starts with the patient’s
presenting symptom(s) which is frequently a
breast mass in 70–90% of cases while 5% present
with pain [9]. Presentation with nipple discharge
is higher in benign lesions (5%) than in malignant disease (1.8%). Other presenting symptoms
include breast enlargement or swelling, skin
Breast Examination
Inspection of the breast is done in supine and
upright positions. This will demonstrate the
breast size, shape, asymmetry, skin or nipple
retraction (dimpling), skin edema (peau
d’orange), erythema, and skin distortion. Breast
palpation will conrm skin or nipple retraction,
breast discharge on squeezing, and presence of a
mass or masses. The axilla is examined for palpable lymph nodes which may be soft, mobile,
and normal as opposed to large, rm, hard, or
xed nodes suggestive of malignancy.
Screening andDiagnostic
Mammography
Mammography Has become a useful tool for
breast screening and diagnosis. It is available
only in large/tertiary medical centers in LMICs
and almost never in district hospitals in rural
areas.
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With the hypothesis that early detection will
improve outcome, medical screening of asymptomatic, apparently healthy women for breast
cancer is very desirable but not readily available
in LMICs. Mammographic screening in the
detection of breast abnormalities reduces breast
carcinoma mortality by nearly 40% with a 30%
increase in overall survival. The most frequently
diagnosed carcinoma by mammography is ductal
carcinoma in situ (DCIS). Utilization of mammographic screening leads to reduction of the size of
invasive breast cancer due to early detection [5].
Women who fail to comply with annual mammography, the usual nding in LMICs, develop
large breast cancers, 50% of which are invasive
tumors compared to smaller size tumors found in
the regularly screened women. Since screening
mammography saves lives, it would be important
to add such a modality to healthcare in underserved rural areas in LMICs.
Guidelines for mammographic screening are
uncertain in LMIC settings. In wealthy countries,
there is no reported benecial effect of screening
mammography in young women under 40 with
no known risk factors for breast cancer. For
women age 40years and older who are at average
risk for breast cancer, recommendation is for
annual clinical breast examination and annual
mammography.
Apart from screening, mammography in
symptomatic patients is to detect synchronous
non-palpable lesions in the ipsilateral or contralateral breast. Figure 30.2 is the magnication
view of diffuse, pleomorphic, clustered microcalcications suspicious for malignancy conrmed by the stereotactic biopsy of this lesion.
It is reported that 15–30% of non-palpable
lesions detected on mammogram that are biopsied are malignant. This approach is facilitated
by the use of standard reporting system recommended by the radiologist, with numerical risk
assessment from 0 (inadequate study) to 5
(highly suggestive of malignancy, action
required).
Ultrasonography (USG) has the advantage of
being more available in LMICs and being easy to
use in the clinic. It is, however, limited by the
experience of the operator. Ultrasound employed
as an adjunct to mammography is especially useful in a dense breast and is very effective in the
differentiation between cystic and solid masses
and in guidance to biopsy. In contrast to benign
masses with sharp, well-dened edges, malignant
masses have irregular margin (Fig. 30.3a, b, c).
USG can show a mass within a cyst in the rare
case of intracystic carcinoma.
Magnetic Resonance Imaging (MRI) Is
infrequently found in LMICs and is expensive.
MRI is another modality of breast imaging
that employs magnetic and radio frequency
fields to visualize intravenously administered
ab c
Fig. 30.2 Magnication right craniocaudal view showing
extensive clusters of microcalcications for which core
needle biopsy was done. Histology was DCIS (a) Right
breast mediolateral view showing microcalcications. (b)
Right breast craniocaudal view showing microcalcications. (c) Stereotactic core needle biopsy specimen
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a
b
c
Fig. 30.3 Real-time ultrasound of the right breast showing: (a) Anechoic, smooth-walled mass which is a simple
cyst. (b) A well demarcated and hypoechoic mass which
is broadenoma. (c) A spiculated mass in left breast which
on core needle biopsy demonstrated inltrating ductal
carcinoma
Gadolinium-DTPA in enhanced breast lesions
due to increased blood flow and capillary permeability. It is 100% sensitive in determining
invasive breast cancer and the sensitivity is not
impaired by dense parenchyma. It can detect
cancers not detected by mammography.
Breast Biopsy
Fine needle aspiration (FNA) is performed in
the clinic under USG guide to aspirate cyst or
biopsy a mass. One uses a 1.5 inch, 22-gauge
needle attached to a 10 or 20 milliliter syringe. A
clear straw-colored aspirate is discarded while
cloudy or bloody uid aspirated from a cyst is
sent for cytology. The material is smeared on
microscope slides that are air dried or xed with
95% ethanol before being sent for cytology.
Vacuum assisted USG-guided core needle
biopsies are performed in the clinic. Unlike
FNA, it is uncomfortable and a 14-gauge needle
is used and the syringe is connected to a vacuum
automated device. The piece of tissue obtained is
put in formalin and sent for histological exam
and immunohistochemistry.
Stereotactic core needle biopsy is performed
as an outpatient procedure in the radiology
department for non-palpable lesions like microcalcications (Fig. 30.2). It is either performed
guided by mammography or by MRI.It is usually
done under local anesthesia because it is very
uncomfortable. Accuracy of this technique is
96–100%.
Open surgical biopsy may be the method of
choice in District Hospitals in LMICs where
mammography or MRI machines are not available. It is an invasive procedure performed under
local anesthesia in the operating room using sterile conditions. It gives the surgeon the opportunity to obtain an adequate tissue sample for
histologic evaluation and diagnostic genetic testing which is available only in major academic
centers in LMICs.
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Benign Breast Disease
The breast is a physiological dynamic structure
with cyclical variations where aberrations of normal development and involution may account for
many, if not all, benign breast disorders
(Table 30.2). Such disorders receive less attention than breast cancer despite reports showing
that benign breast disease is an important risk
factor for breast cancer. Women with nonproliferative lesions, proliferative ndings but no
atypia, and those with atypical hyperplasia have a
relative risk of breast cancer of 1.27, 1.88, and
4.24, respectively. Classication of benign
lesions is based on whether the biopsy is proliferative, non-proliferative atypia on histology
with atypia being the most worrisome.
Fibrocystic breast disease is a nonspecic
disorder which occurs in response to cyclic hormonal stimulation of the breast. It has been
described as chronic cystic mastitis, brocystic
changes, or cystic mastopathy. Patients may present with breast pain (mastodynia), breast mass, or
nipple discharge. Patients are reassured that there
is no evidence of cancer and some might need
treatment for mastodynia.
Cyclical mastalgia [Mastodynia] is a common presentation in women with benign breast
disease. Pain usually correlates with menstrual
cycle, waxes and wanes, and is usually bilateral.
The breast exam conrms tender, nodular breasts.
Mastalgia is caused by either increased estrogen
or decreased progesterone production, abnormal
prolactin secretion, or psychogenic disorder. Pain
relief is dependent on the use of any of the following: diuretics, progesterone, anti-estrogen
(tamoxifen), antigonadotrophin suppression
(danazol), or essential fatty acid (primrose).
Cysts are an aberration of normal lobular
physiology and can be single or multiple. The
common presenting symptom is a breast mass
which may be palpable and well demonstrated on
USG (Fig.30.3a). Patients can be safely observed
if the cyst is small or aspirated with a ne needle
when it is large. Cytological examination should
be obtained when the uid is bloody but is not
Table 30.2 Pathogenesis of Benign breast diseases
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useful if it is clear. Cystic lesions do not need
excisional biopsy unless the uid is bloody, the
cyst persistently rells X 3, or there is a residual
mass after aspiration.
Fibroadenoma is the most common breast
lesion in nulliparous adolescents and young
women. The peak age incidence of the disease is
16–25 years [10]. Of interest is the nding that
broadenoma is more frequent than brocystic
disease and cancer in blacks in the USA [9],
Africa [10], and the West Indies [11]. In contrast,
the order of occurrence of breast neoplasm in a
predominantly white population is brocystic disease, cancer, and broadenoma [6]. Fibroadenoma
generally presents as either a painless, enlarging
breast mass or multiple unilateral or bilateral
breast masses in 15% of patients [9]. It is easily
distinguished from a cyst with breast USG
(Fig.30.3). The mass is usually observed and not
excised in women under 30years of age unless it
rapidly enlarges or becomes painful which may
Fig. 30.4 A 26-year-old Nigerian woman with a right
breast cystosarcoma phyllodes
occur with pregnancy. If the cytology report is not
diagnostic on the FNA of the mass, an excisional
biopsy is performed.
Fibroadenoma may grow in size and become
giant broadenoma which is referred to as cystosarcoma phyllodes (Fig.30.4). A few may ll up
the breast and mastectomy may be indicated.
Galactocele is a breast cyst lled with milk
and is frequently seen during lactation or after
cessation of breast feeding. The patient presents
with a breast mass which is most often painful.
USG delineates the mass and mammography is
rarely indicated. Treatment is needle aspiration of
the cyst containing milk.
Sclerosing adenosis: Is a benign condition
that is easily confused with breast cancer on
mammography because its appearance is similar
to that of radial scar. The recommended treatment is excisional biopsy.
Intraductal papilloma may be solitary or
multiple and frequently presents with a history of
spontaneous nipple discharge. The discharge can
be serous, blood-tinged, or bloody. The lesion
can be demonstrated on ductogram and is treated
with excisional biopsy. Solitary papilloma does
not increase the risk of breast cancer like multiple
or diffuse papillomatosis [6].
Atypia can be ductal or lobular hyperplasia
and is only an incidental pathological nding
without clinical and mammographic features.
Atypia carries a risk factor of 4–5 for breast cancer compared to the general population. It is
treated by needle localization and excisional
biopsy.
Lobular carcinoma in situ (LCIS) is also an
incidental pathological nding that lacks clinical
and mammographic features. It is an uncommon
disorder that has a high (8–10) risk factor for
development of bilateral breast cancer. Women
with LCIS are closely monitored with digital
breast exam every 4–6months and mammography 12 to 18 months. Bilateral prophylactic
mastectomy is an alternative treatment for women
who are unwilling to take the risk of developing
breast cancer.
Disorders of the nipple are identied by nipple discharge which may be physiological or
pathological. The discharge may be milky,
serous, greenish, blood tinged, or bloody. Only
bloody nipple discharge raises the question of
neoplastic disease while the others are associated
with lactation, prolactinoma, and brocystic dis-
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ease. All patients with nipple discharge are evaluated with USG and mammography. It is
recommended that the draining duct in women
with bloody nipple discharge be excised for histological examination for intraductal papilloma
or cancer.
Other benign lesions of the nipple include
nipple inversion which is congenital and nipple
retraction which may be caused by duct ectasia,
cancer, or previous surgery. Accessory nipples
are almost always benign.
Breast Infection
Breast Infection Can Occur during
Lactation or May beSpontaneous
Lactational Breast Abscess The incidence
of pyogenic breast abscess is high in Africa
where breast feeding is commonly practiced
until the child is 2–3years old [10]. The infection starts as a localized area in the breast that
becomes painful, red, tender, and indurated.
When the patient is seen early, the infection
can be treated with antibiotics, suspending
breast feeding on affected breast, and observation. Occasionally, acute mastitis may
progress into an abscess. The patient presents
with fever and a warm, tender, fluctuant mass
in the breast. The abscess is usually secondary
to cracked nipple or breast engorgement at
weaning. The abscesses are peripherally
located and can be treated with antibiotics and
repeated needle aspirations. Incision and
drainage may be necessary to drain and
debride necrotic tissue in large abscesses
which when neglected are associated with
overlying skin necrosis.
Nonlactational or spontaneous breast
abscess begins as a tender periareolar mass that
frequently has a high incidence of recurrence.
The initial treatment is incision and drainage
with antibiotics to clear the surrounding cellulitis. The antibiotic of choice is based on previous
culture studies, and if the infection becomes
recurrent, the treatment requires excision of the
diseased ducts.
Malignant Breast Diseases
Despite new approaches to breast cancer screening that includes the use of molecular markers
and magnetic resonance imaging, breast cancer
remains the most frequently diagnosed cancer in
women worldwide, and the second most common
cause of cancer deaths in the USA.The female to
male incidence ratio is 99 to 1. The breast cancer
mortality rate continues to decline. The mortality
rate in the USA is 40% higher in blacks compared to whites (28.4 vs 20.3 deaths per 100,000)
[12]. This disparity is more pronounced among
African American women who are younger than
50years in whom mortality is 77% higher compared to white women. Use of race/ethnicity in
our discussion is a sociopolitical construct without any anthropologic implications. A Black or
African American is a person who has origins in
any black racial groups of Africa. A White is a
person having origins in any of the original peoples of Europe, the Middle East, or North Africa.
Breast Cancer Risk Factors
Although the identication of the BRCA1/
BRCA2 and PALB2 gene mutations has contributed greatly to understanding the cause of familial forms of breast cancer in 5–10% of breast
cancer risks, we still do not have explanation for
all the causes of the remaining 90% of sporadic
breast cancer. It is estimated that 20–30% of sporadic breast cancers are familial. And it is hypothesized that most sporadic breast cancers are likely
to be polygenetic disorders involving multiple
genes. A number of studies have recently shown
that sporadic breast cancer is closely related to
duration of exposure of the breast to estrogens
[13]. In general, the risk factors leading to the
development of breast cancer include:
• Family history of breast cancer: 5–10% of
breast cancers are associated with proven
genetic predisposition for the disease, while
20–30% have a strong family history of breast
cancer. The markers in high-risk families
include involvement of multiple generations
and rst degree relatives, occurrence in pre-
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menopausal women, and history of bilateral
breast disease and ovarian cancer.
• Personal history of breast cancer: A woman
with history of cancer in one breast is more
likely than the general population to develop a
new cancer in the contralateral breast.
• Benign breast disease: Atypical hyperplasia
and lobular carcinoma in situ increase the risk
of breast cancer.
• Overexpression of estrogen receptors:
Overexpression or exposure of the receptors
to estrogen in normal breast epithelium augments [13] the risk factor for breast carcinoma
in the following settings: (1) older age; (2)
early age menarche; (3) nulliparity; (4) late
age of rst full term pregnancy; (5) breast
feeding; (6) overweight and morbid obesity;
(7) post-menopausal hormone therapy; (8) use
of oral contraceptives; (9) later age at menopause; (10) number of years since last birth;
(11) increased interval between menarche and
birth of rst child; and (12) years of education
(may delay child birth).
• Inherited germline mutations (BRCA1/2,
PALB2, and BRIP1/MCPHI) are associated
with 5–10% of breast cancers. Women with
BRCA 1/2 mutations have up to 85% risk of
developing breast cancer during their lifetime.
The majority of these women develop cancer
before the age of 50years. Additionally, cancers in women with BRCA 1/2 mutation are
aggressive and display high histologic grade,
triple negative, and HER2/Neu immunophenotype. And these women are at high risk of
developing ovarian cancer. Men with BRCA
mutation are at high risk of developing breast
and prostate cancer [14]. Besides BRCA,
mutations in PALB2, BRIP1/MCPHI,
RAD51C and RAD41D, and others are associated with hereditary breast cancer. Of note,
PALB2 mutation is also associated with pancreatic cancer while BRIPI/MCPHI mutation
is associated with ovarian cancer.
• TP53 mutation (Li-Fraumeni syndrome) is
very rare and increases incidence of hereditary
breast cancer in less than 1% of women.
• Radiation exposure for treatment of other
diseases during the rst three decades of life is
strongly linked to breast cancer.
Breast Cancer Biological
Characteristics
Recent advances in clinical practice, radiology,
immunohistochemistry, and molecular biology
have shed some insight in the development of
cancer. A review of the literature indicates that
hormonal receptors, genetic mutations, irradiation, and other factors increase breast cancer risk
in women. This complex subject is extensive and
is only briey discussed here.
Molecular Subtypes
Historically, female breast cancer mortality has a
bimodal age distribution with early and late age
at diagnosis. Early age breast cancer is hormonedependent and the peak age incidence is at 50,
whereas the second breast cancer type is
hormone- independent and has a peak incidence
at age 60 [7]. Recently, use of immunohistochemistry has shown that the etiologies of these
two age based groups of breast cancer are different. They can be further separated into four
molecular subtypes according to hormone receptor expression (HR) and/or human epidermal
growth factor receptor 2 (HER2/Neu also referred
to as ERBB2) expression. The molecular subtypes are referred to as luminal A {HR+/HER2-),
luminal B (HR+/HER2+), HER2 enriched (HR-/
HER2+), and triple negative (HR-/HER2-).
These are signicant for the choice of hormonal
and/or chemotherapy.
Incidence rates for triple-negative breast cancer subtype with the worst prognosis are twice as
high among black women compared to white
women [7, 12]. In Blacks, incidences of HR+/
HER2+, HR-/HER2+, and triple-negative subtypes are signicantly higher than in nonHispanic white women. Compared to
non-Hispanic white women, Asian/Pacic
Islander women have higher incidence of HR-/
HER2+ but lower incidences of HER+/HER2and triple-negative subtypes.
Histological grades rely on degree of tumor
differentiation varying from well differentiated to
undifferentiated. Tumors with a high grade are
aggressive and have poor prognosis. The recent
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