Case Report

A WOMAN 49 YEARS OLD WITH

CARCINOMA MAMMAE SINISTRA

By :
Bramasta AgraG99161028
Dyah Candra Dewi G99162159
Alyssa Amalia G99162077
Mega Hasenda
Afifah Syifa

Advisor :

dr. Kristanto Yuli Yarsa, Sp.B(K)Onk.

KEPANITERAAN KLINIK SMF ILMU BEDAH

FAKULTAS KEDOKTERAN UNS/RSUD DR. MOEWARDI
SURAKARTA
2017

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 PATIENT STATUS

I. ANAMNESIS
A. Patient Identity
Name : Miss. R
Age : 49 years old
Sex : Woman
Religion : Islam
Job : Farmer
Address : Sukoharjo, Jawa tengah
Martial state : Married
Date of hospitalized : 17 Juli 2017
Date of examination : 18 Juli 2017

Medical Record number : 0134xxxx

B. Chief complain
Lumps on left mammae

C. Present illness
Patient complained about a lump in her left breast that she has felt
since one year ago. The lump has always been the same size, there isn't
any tenderness, but sometimes the patient feels the pain in the lump that
suddenly happens and it occurs for the short time. The patient has not
any complaints about the lump in her neck and shoulder, abnormal
secretion from her breasts, lesions in her breasts, breathlessness,
headache, pain in her back or bones, chronic cough, stomach pain, loss
of weight, and the loss of appetite. She sought for treatment to RSUD
Sukoharjo; she had the examination and chest USG there. Because of the
lack of facility, the patient was referred to RSDM for further
examination and treatment.

D. Past ilness
Historical history : denied
Hypertension history : denied
Diabetes mellitus history : denied
Asthma history : denied
Allergy history : denied
History of heart disease : denied

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 Hospitalized history : (+) 1 years before admission with
pemphigus vulgaris

E. Family disease history

Historical history : denied
Hypertension history : denied
Diabetes mellitus history : denied
Asthma history : denied
Allergy history : denied
History of heart disease : denied

F. Social and Economic History

Patients work as farmer. Patients are currently treated in RSDM

with BPJS facility.

G. History of Nutrition and Habitual

Patients eat 3 meals a day with rice and side dishes.Nafsu makan
sehari-hari baik. History of alcohol consumption, smooking, regular
excercise was denied.

H. History of obstetric and gynaecology

Birth History : 3 times, per vaginam. First child was born

when patient at 20 years old

Menarche History : patient first menarche at 15 years old,

menarche cycle were not regular between 2
days in a week or 7 days in a week with only
spots menarche.
Breastfeeding history : all of her child receive breastmilk for 2 years

Contraception history : (+) contraception pills for ± 25 years

I. Systemic history
Skin : dry (-), pale (-), thickened (-), itch (-), yellow (-)
Head : headache (+), dizziness (-)

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 Eyes : blurred (-), yellow (-), double view (-)
Nose : cold (-/-), nasal congestion (-), blood out (-)
Ears : reduced hearing (-), ring (-) fluid out (-)
Mouth : sore gums (-), dry mouth (-)
Throat : swallowing (-), hoarseness (-)
Respiration : Shortness of breath (+), cough (-)
Cardiovascular : palpitations (-), chest pain (-)
Mammae : Lumps (+) mammae sinistra, pain (-) peau
d’orange (+), nipple retraction (+)
Gastrointestinal : nausea (-), vomiting (-), abdominal pain (-)
Musculoskeletal : pain (-)
Genitourinaria : pain urination (-), Bloody urination(-), frequent
urination (-)
Extremities
Above : wound (- / -), fingertips are cold (- / -),
swelling (- / -) Weak (- / -), pain (- / -)
Below : wound (-/-), fingertips are cold (- / -),
swelling (- / -), Weak (-/-), pain (+/-)

II. Physical Examination

A. General circumstance
a. General circumstance : compos mentis, E4V5M6, medium pain,
karnofsky score 60%
b. Vital sign :
BP : 130/80 mmHg
HR : 78x/menit
RR : 13x/menit
T : 36,7o C

B. General Survey
a. skin: ikterik (-), dry (-), hyperpigmentation (-)
b. Head: mesocephal, sunken crown (-).
c. Eyes: pale conjunctiva (- / -), sclera ikterik (- / -), concave (- / -)
d. Nose: secretions (- / -), nasal congestion (-)
e. Ear: reduced hearing (-), ringing (-) out the liquid (-)
f. Mouth: wet mucosa (+), cyanosis (-)
g. Neck: KGB enlargement (-), JVP R + 2 cm

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h. Mammae :
Dekstra :
Inspection : retraction (-), skin color change (-), peau d orange
(-), secret (-),
Palpation : lumps (-)
Sinistra :
Inspection : lumps (+), nipple retraction (+), skin color
change (+) arround areola, peau d orange(+),
secret (-)
Palpation : mass palpable hard, fixed, strict lines, measure
3 cm x 2cm, single nodule, pain (-)

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6
 i. Lymph gland :
Axilla right and left : mass (+) left lymph gland axilla, single nodule,
hard, measure 1x1 cm, pain (-)
Infraclavicula right and left: mass(-), pain (-)
Supraclavicula right and left : mass (-), pain (-)
Mammaria interna : mass (-), pain (-)
j. Cor
I: ikcus kordis not visible
P: ikcus kordis not strong lift
P: limit the impression widened heart (-)
A: Heart Sound I-II int. Normal, regular, noisy (-)
k. Pulmo
I: symmetrical chest development (+), retraction (-), swelling (-)
P: Fremitus touches the right>left, Tender (-), crepitation (-)
P: sonor / sonor decrease in SIC VII
A: normal vesicular / vesicular voices decrease from
costae VII, additional sound (- / -)
l. Abdomen
I: abdominal wall parallel to the chest wall, distension (-)
A: bowel sounds (+) 8x / min
P: timpani, undulation (-)
P: tenderness (-), palpable liver (-), palpable lien (-)Genitourinaria
: BAK normal, Nyeri ketok costo vertebra (-)
m. Ekstremitas : CRT < 2 second
Cold Acumen Oedema
- - - -
- - - -

III. Support Examination

a. Blood examination 10 July 2017 at RSDM Surakarta

Examination Result Unit Reference

Hemoglobin 12.1 g/dL 12,0 – 15,6

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Hematokrit 38 % 33 – 45
Leukosit 10.7 Ribu/µl 4,5 – 11,0
Trombosit 308 Ribu/µl 150 – 450
Eritrosit 4.56 Juta/µl 3,8 – 5,8
PT 13 detik 10,0 – 15,0
APTT 25.6 detik 20,0 – 40,0
GDS 99 Mg/dL 60 – 140
SGOT 22 u/L < 31
SGPT 28 u/L < 34
Creatinin 0,9 Mg/dL 0,6 – 1,1
Ureum 39 Mg/dL < 50

b. USG examination 19 October 2016 at RSUD Sukoharjo

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Result : Solid mass mammae sinistra longitudinal oval 2,37 x 3,53 cm,
susp malignancy

c. X-Ray examination 20 October 2016 at RSUD Sukoharjo

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Result : There is no metastases right and left lung

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IV. ASSESSMENT
Carcinoma mammae sinistra

V. PLAN
- FNAB
- Mammografi

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1.

LITERATURE REVIEW

A. Anatomy of the Breast

Mammary gland (glandula mammaria s. mamma) is a pair organ, which

relates to the type of the apocrine glands of the skin. It mostly occurs at the base
on the large breast muscle (m. pectoralis major), partially on the front of ridge‐
shaped muscle (m. serratus anterior) and crossing the free edge of breast muscle,
adjoins by its small section to the side of breast wall. In the average the base of
gland reaches the external edge of sternum. The mammary gland is usually
located at the level of the III to (VI) VII ribs, and from all sides (except the nipple
and aerola) is surrounded by fatty tissue. Between both mammary glands there is a
deepening called cavity (sinus mammarum).

Fig 1.1 Anatomy healthy breast

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 Innervation of the Breast In the past, the innervation of the breast received
little attention in anatomic textbooks, and published reports were contradictory
concerning the distribution and course of the supplying nerves. The British
surgeon Sir Astley Cooper was one of the first to investigate the innervation of the
breast 135 years ago, and some of his findings are still valid today. Ever since,
authors have agreed that the skin of the breast and the gland is innervated by the
lateral and anterior branches of the intercostal nerves; however, there is wide
disagreement about which intercostal nerves are involved.
Innervation of the Gland and the Breast Skin The breast is innervated by the
lateral and anterior cutaneous branches of the second to sixth intercostal nerves.
The lateral cutaneous branches pierce the intercostal muscles and the deep fascia
in the midaxillary line and take an inferomedial course. The second lateral
cutaneous branch terminates in the axillary tail of the breast. The third, fourth,
fifth, and sixth lateral cutaneous branches continue on the surface of the serratus
anterior for 3–5 cm. At the border of the pectoral muscle they divide into a deep
and a superficial branch. The deep branch courses below or within the pectoral
fascia to the midclavicular line, where it turns for almost 90° to run through the
gland, giving off several branches (Figs. 1.2). The superficial branch runs in the
subcutaneous tissue and terminates in the skin of the lateral breast (Figs. 1.2). The
anterior cutaneous branches innervate the medial portion of the breast. After
piercing the fascia in the parasternal line they divide into a lateral and a medial
branch. While the medial branch crosses the lateral border of the sternum, the
lateral branch divides again into several smaller branches, which take an
inferolateral course through the subcutaneous tissue. They become progressively
more superficial along their way and terminate in the breast skin or at the areolar
edge. The supraclavicular nerves terminate in the skin of the superior part of the
breast.

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 Fig. 1.2. Schematic drawing of breast and anterior (ACB) and lateral cutaneous branches
(LCB) of fourth intercostal nerve innervating the nipple and areola. (Reprinted with
permission from Lippincott, Williams and Wilkins: Plast Reconstr Surg 105:905, 2000).

Blood Supply of the Breast Arterial System Three main arterial routes supply
the breast: the internal mammary artery, the lateral thoracic artery, and the
intercostal arteries (Fig. 1.3).
The internal mammary artery, a branch of the subclavian artery, provides
approximately 60% of total breast flow, mainly to the medial portion, by anterior
and posterior perforating branches. The anterior perforating branches exit their
respective intercostal spaces approximately 2 cm laterally to the sternum. The
second and third anterior perforating branches are by far the most significant. The
first and fourth are less constant. They course inferiorly and laterally to
anastomose with branches of the lateral thoracic artery at the nipple. The posterior
perforating branches exit more laterally from the intercostal spaces and supply the
posterior aspect of the breast.
The lateral thoracic artery arises from the axillary artery or, rarely, from the
thoracoacromial or subscapular artery. This artery supplies up to 30% of breast
blood flow to the lateral and upper outer portions of the breast. The branches
course inferomedially within the subcutaneous tissue to effect anastomoses with
branches of the internal mammary and intercostal arteries in the areolar area.

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 The third, fourth, and fifth posterior intercostal
arteries are the least important of the arteries supplying
the breast. Originating from the aorta, they course in the
intercostal spaces and mainly supply the inferoexternal
quadrant of the breast. Additional minor sources of
arterial supply to the breast include branches from the
axillary artery, the thoracic artery, the subscapular artery,
and the pectoral branches of the thoracoacromial artery.
(Lippincot, 2000)

Fig. 1.3. Three main arterial routes supplying the breast: internal mammary artery (IM),
lateral thoracic (LT) artery, and intercostal (IC) arteries

Four Quadrants of the Breast

1. Upper outer(superolateral) quadrant
2. Upper inner(superomedial) quadrant
3. Lower outer(inferolateral) quadrant
4. Lower inner(inferomedial) quadrant

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 Fig. 1.4. Four Quadrants of the Breast
B. Histology of the Breast

The breast is composed of glandular and stromal tissue. Glandular tissue

includes the ducts and lobules. Stroma comprises area between lobes.

Fig. 1.5 Histology of the Breast

Life cycle changes histology of breast between pre-puberty until menopause.

Pre-puberty, lactiferus ducts are formed at birth but lobules renai underdeveloped
until pubery. Puberty, ovarian estrogen and progesterone induces branching of
ductal system and development of lobules. In pregnancy, progesterone and
prolactin induce complete maturation of breast at the time of full-term pregnancy,
permanent increase in number and size of lobulesm oxytocin induces
myoepithelial proliferation and differentation, following lactation total breast size
decreases due to apoptosis of epithelium and lobule atrophy. When aging and
menopause, lobular and ductal atrophy occurs, interloblar stroma decreases in
fibrous connective tissue and increases in adipose tissue content (Pandya, 2011).
The lymph system is a network of lymph (or lymphatic) vessels found
throughout the body. The lymph vessels carry lymph fluid and connect lymph
nodes. Lymph nodes are small, bean-shaped collections of immune system cells.

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Lymph vessels are like small veins, except that they carry a clear fluid called
lymph (instead of blood) away from the breast. Lymph contains tissue fluid and
waste products, as well as immune system cells.

Fig. 1.6. Lymph system of the breast

C. Risk Factor of Breast Cancer

1. Gender
Female: Primary risk factor. Lifetime risk in females is 1:8 compared to
males at 1:1000 (Michels, 2006).
2. Age
Aging: Risk increases with advancing age. Risk at age 40 is 1:217 and
risk at age 80 is 1:10.
3. Height and weight
Height: Taller women, both pre- and postmenopausal, have a slightly
increased risk; likely correlated with hormonal stimulation (Ottini et al, 2010)
Weight: High body-mass index (BMI) is a risk factor for postmenopausal
women, likely due to adipose tissue production of estrogen via aromatase.
High BMI may lower risk for premenopausal breast cancer due to anovulation

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(see Polycystic ovarian syndromechapter) and reduction of circulating
estrogen and progesterone (Ahn, 2007).
4. Medical history
History of benign proliferative breast disease: Previous breast biopsy
showing proliferative changes, particularly with atypical epithelial cells.
History of cancer: Previous history of breast, endometrial or ovarian
cancer.
5. Reproductive history
Early age (<12) at menarche and late age (>55) at menopause: Risk
increases linearly with the cumulative number of ovulatory cycles.
Proliferation of breast epithelium occurs in the luteal phase of the ovulatory
cycle, thereby increasing risk of promotion of initiated cells.
Late age (>35) of first full-term birth and nulliparity: Pregnancy induces
terminal differentiation of luminal cells by exposing the tissue to human
chorionic gonadotrophin (hCG). Breast gene expression changes permanently
after pregnancy, increasing DNA repair pathways and control over apoptosis.
However, pregnancy itself causes a transient risk of breast cancer because of
increased estrogen and progesterone exposure, which promotes proliferation
in initiated cells. Late age at first full-term birth increases time for exposure
to carcinogens (Russo, 2011).
6. Exposure history
Hormone replacement therapy (HRT): Combined estrogen and
progesterone therapy has been linked to the development of breast cancer in
postmenopausal women; not estrogen alone. Oral contraceptives (OCP) do
not increase risk. Estrogen and progesterone in HRT likely promotes
preneoplastic lesions rather than initiate them. Since OCP is used in younger
women, the number of preneoplastic lesions is much lower than in
postmenopausal women, rendering the OCP risk much lower (Narood, 2011).
Ionizing radiation: Breast tissue is sensitive to carcinogenic effects of
radiation. Risk is highest in the developing breast and absent after menopause
(Ronckers, 2005).

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 Smoking: First hand smoking at a young age as well as before a first full
term pregnancy. Smoking allows tobacco carcinogens to initiate breast cells
prior hormonal stimulation during young adulthood and pregnancy. Cigarette
smoke contains at least 20 carcinogens that are known to transform breast
cells (Luo et al, 2011).
Alcohol: Alcohol has been shown to increase the amount of circulating
estrogen, possibly by decreasing hepatic metabolism, increasing aromatase
activity, or increasing adrenal sex hormone production (Chen et al, 2011).
7. Family history
Affected first-degree relatives: Risk increases with number of affected
relatives, especially with early-onset breast cancer, bilateral breast cancer or
male breast cancer.
Breast cancer predisposition syndromes
Hereditary breast and ovarian cancer (HBOC) syndrome: Associated
germline mutation intumour suppressor genes BRCA1 and BRCA2 involved
in homologous DNA repair. 5-10% breast cancer cases are considered directly
related to inheritance of mutations in BRCA1 or BRCA2. Women carrying
mutations in BRCA1/2 genes have a 50-80% lifetime risk of breast cancer.
BRCA1 gene is located on chromosome 17q21 and is classified as a
tumour suppressor gene. It functions as a pleiotropic DNA damage repair
protein. Its mutation is associated with basal-like phenotype of breast cancer,
high grade III subtype, high mitotic count, and triple negative (ER/PR/HER2)
carcinomas.
BRCA2 gene is located on chromosome 13q12 and also classified as a
tumour suppressor gene; though shares no homology with the BRCA1gene.
However, it can bind with BRCA1 to participate in DNA damage response
pathway. BRCA2 protein functions as a mediator of the core mechanism of
homologous recombination. Its mutations are linked to breast carcinomas that
are ER and PR positive. Though rarely associated with basal-like phenotype
but still linked to a higher grade (II or III) when compared to age-matched
sporadic cases.

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 Cells lacking BRCA1/2 are much more sensitive to ionizing radiation,
suggesting a role for BRCA1/2 in DNA damage response (DDR), specifically
in repairing double-strand breaks (DSB), which is the major lesion inflicted
by ionizing radiation.
Li-Fraumeni syndrome: Characterized by early onset breast cancers,
sarcomas, brain tumours, adrenal cortical tumours and acute leukemias.
Associated germline mutations in the TP53* gene. (lifetime risk = 90%)
Cowden syndrome: Characterized by high rate of breast cancer and
mucocutaneous findings, thyroid disorders and endometrial carcinomas.
Associated germline mutations in the PTEN* gene. (lifetime risk = 50%)
(Roy and Chun, 2011).

D. Pathogenesis

1. Gene expression in breast carcinomas

Two different types of estrogen receptors exist, alpha (α) and beta (β)
(ERα and ERβ respectively). Various tissues express these receptors with
breast, ovaries and the endometrium expressing ERα, while the kidneys,
brain, lungs and several other organs expressing ERβ. The role of ERβ in
carcinogenesis remains controversial whereas, a clear contribution of ERα
protein has been established.
Both ER subtypes carry a DNA binding domain and exist in the nucleus
and the cytosol. When estrogen enters the cell, it binds the ER and the
complex migrates into the nucleus and leads to the production of transcription
proteins that induces changes in the cell. Therefore, due to estrogen’s
proliferative properties, its cellular stimulation can have negative
consequences in patients expressing large quantities of these receptors
intracellularly.
2. Role of estrogen in breast cancer progression and development
Two major hypotheses attempt to explain the tumorigenic effects of
estrogen: (i) genotoxic effects of estrogen metabolites via generation of

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 radicals (initiator) and (ii) the hormonal properties of estrogen inducing
proliferation of cancers as well as the premalignant cells (promoter).
3. Role of Human Epidermal Growth Factor Receptor 2 (HER2)
HER2 belongs to the epidermal growth factor receptor (EGFR) family of
proto-oncogenes and currently is not known to have a ligand. However, the
protein has been shown to form clusters within the cell membranes in
malignant breast tumours. Its mechanism of carcinogenesis remains largely
unknown, but overexpression is associated with rapid tumour growth,
shortened survival, increased risk of recurrence after surgery, and poor
response to conventional chemotherapeutic agents (Yager, 2006).

E. Diagnosis

History and physical examination

The clinical history is directed at assessing cancer risk and establishing the
presence or absence of symptoms indicative of breast disease. It should include
age at menarche, menopausal status, previous pregnancies and use of oral
contraceptives or post-menopausal hormone replacements. A personal history of
breast cancer and age at diagnosis, as well as a history of other cancers treated
with radiation. In addition, a family history of breast cancer and/or ovarian cancer
in a first- degree relative should be established. Any significant prior breast
history should be elucidated including previous breast biopsies. After the
estimated risk for breast cancer has been determined (see above), the patient
should be assessed for specific symptoms like breast pain, nipple discharge,
malaise, bony pain and weight loss.
Physical examination should include a careful visual inspection with the
patient sitting upright. Nipple changes, asymmetry and obvious masses should be
noted. The skin must be inspected for changes such as; dimpling, erythema, peaud'
orange (associated with local advanced or inflammatory breast cancer). After
careful inspection and with the patient in the sitting position the cervical,
supraclavicular and axillary lymph node basins are palpated for adenopathy. When

24
palpable the size, number and mobility should be ascertained. Palpation of the
breast parenchyma itself is performed with the patient supine and the ipsilateral
arm placed over the head. The subareolar (central quadrant) and each quadrant of
both breasts is palpated systematically. Masses are noted with respect to their size,
shape, location, consistency and mobility.

Multistep approach:
1) Patients are identified by screening or symptoms.
2) Imaging is done by either ultrasound or mammography.
Mammogram has a false negative rate of 11%. It is accurate in detecting
calcifications as well as small non-palpable lesion in postmenopausal women
with non-dense breast tissue.
Ultrasound is better at detecting fluid-filled lesions (cysts) and small tumours
in dense breast tissue.
3) Biopsy or fine needle aspiration is done if a lump is detected by imaging or if
clinically it appears suspicious.
4) Pathological diagnosis distinguishes benign and malignant breast disease.
Staging is done using the TNM system (see Introduction to neoplasia chapter),
but molecular markers (see above) correlate better with prognosis (Bevers et al,
2009).

Clinical features
Table. 1 Very few clinical signs and symptoms exist for breast cancer raising the
importance of screening tests in diagnosis.

Signs and symptoms Characteristics

Benign Malignant

Breast mass – a dominant mass is a distinct Absence of discrete Discrete lump

mass that is asymmetric with the other lump Fixed
breast. Benign findings are often associated Mobile Firm

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with cysts, fibroadenomas, or fibrocystic Soft Irregular borders
changes. Malignant disease often has Smooth borders Non-tender
abnormal cell proliferation and Tender
calcifications, manifesting as a fixed, firm
mass with irregular borders. Any suspicious
dominant mass should undergo diagnostic
tests (see below).

Nipple discharge – usually benign, but Milky, green or yellow Bloody or serous
discharge with blood, from a single duct, or Multiple duct Single duct
associated with breast mass raises Produced with manual Produced
probability of cancer. expression spontaneously

Mastalgia (breast pain) – rarely the Bilateral Focal

presenting symptom of breast cancer Diffuse
Worse during the late
Cyclic mastalgia: Hormonal changes during luteal phase of menstrual
the menstrual cycle trigger an increase in cycle
breast size and volume. Subsides with onset of
menstruation

SOB/dyspnea Metastatic disease to the lungs

Bone pain and symptoms of hypercalcemia Bone metastasis

Abdominal distention and jaundice Liver and peritoneal metastasis

Altered cognitive function and local Brain metastasis

neurological signs
(Meisner et al, 2008)

Table 2 American Joint Commission on Cancer guidelines–tumor node metastasis

classification

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Primary tumor (T)
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
Tis (DCIS) Ductal carcinoma in situ
Tis (DCIS) Lobular carcinoma in situ
Tis (Paget’s) Paget’s disease of the nipple
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 to the skin
(ulceration or skin nodules)
T4a Extension to the chest wall, not including
only pectoralis muscle
adherence/invasion
T4b Ulceration and/or ipsilateral satellite
nodules and/or edema (including peau
d’orange) of the skin, which do not meet
the criteria for inflammatory carcinoma
T4c Both T4a and T4b
T4d Inflammatory carcinoma
Regional lymph nodes (N)
NX Regional lymph nodes cannot be
assessed (for example, previously
removed)
N0 No regional lymph node metastases
N1 Metastases to movable ipsilateral level Ⅰ,
Ⅱ axillary lymph node(s)
N2 Metastases in ipsilateral level Ⅰ, Ⅱ axillary

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 lymph nodes that are clinically fixed or
matted; or in clinically detected ipsilateral
internal mammary nodes in the absence
of clinically evident axillary lymph node
metastases Metastases in ipsilateral level
Ⅰ, Ⅱ axillary lymph nodes fixed to one
another (matted) or to other structures
N2a Metastases only in clinically detected
ipsilateral internal mammary nodes and
in the absence of clinically evident level
I, II axillary lymph node metastases
N2b
N3 Metastases in ipsilateralinfraclavicular
(level Ⅲ axillary) lymph node(s) with or
without level Ⅰ, Ⅱ axillary lymph node
involvement; or in clinically detected
ipsilateral internal mammary lymph
node(s) with clinically evident level Ⅰ, Ⅱ
axillary lymph node metastases; or
metastases in ipsilateral supraclavicular
lymph node(s) with or without axillary or
internal mammary lymph node
involvement
N3a Metastases in ipsilateralinfraclavicular
lymph node(s)
N3b Metastases in ipsilateral internal
mammary lymph node(s) and axillary
lymph node(s)
N3c Metastases in ipsilateral supraclavicular
lymph node(s)
Distant metastases (M)
M0 No clinical or radiographic evidence of
distant metastases

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cM0(i +) No clinical or radiographic evidence of
distant metastases, but deposits of
molecularly or microscopically detected
tumor cells in circulating blood, bone
marrow, or other nonregional nodal tissue
that are no larger than 0.2 mm in a patient
without symptoms or signs of metastases

M1 Distant detectable metastases as

determined by classic clinical and
radiographic means and/or histologically
proven larger than 0.2 mm

Table 3 Clinical staging-

American Joint
Commission on Cancer
guidelines

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F. Diagnostic Imaging

The initial choice of imaging should be individualized to each patient based on the
age and characteristics of the lesions. Diagnostic imaging and image-guided
needle biopsies play a central role in the diagnosis, treatment planning, and
staging of patients with breast cancer.
Mammography
Mammography remains the mainstay in breast cancer detection
(Smetherman DH, 2013). Diagnostic mammograms are performed in
women who have a palpable mass or other symptom of breast disease, a
history of breast cancer within the preceding 5 years, or have been recalled
for additional imaging from an abnormal screening mammogram. Diagnostic
mammograms include special views such as focal compression of one area of
the breast tissue or magnification images. The breast imaging reporting and
database system (BI-RADS) is the standardized method for reporting of
mammographic findings.
Carcinomas present as masses, asymmetries, and calcifications (Table 1).
By definition, a mass is a space-occupying lesion seen in two different planes.
This is distinguished from a density, which is seen only in a single plane. The
shape of masses is described as round, oval, lobular, or irregular, while the
margins are identified as circumscribed (with welldefined margins),
indistinct, and spiculated (with densities radiating from the margins).

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Calcifications associated with benign disease are generally larger than those
seen with malignancy and typically are coarse (round, lucent centered, or
“layering” on medial lateral or lateral medial images). Clustered amorphous,
indistinct, pleomorphic (or heterogeneous), or fine, linear, or branching
calcifications are more typical of carcinomas.
MRI
Breast MRI has become an integral part of breast cancer diagnosis and
management in selected patients. Current indications for breast MRI include
evaluation of patients in whom mammographic evaluation is limited by
augmentation (including silicone and saline implants and silicone injections),
determining the extent of disease at the time of initial diagnosis of breast
cancer (including identification of invasion of the pectoralis major, serratus
anterior, and intercostal muscles), evaluation of inconclusive findings on
clinical examination, mammography, and/or ultrasonography, screening of the
contralateral breast in selected patients with newly diagnosed breast
carcinoma, and asymptomatic screening of patients at very high risk of breast
carcinoma (in conjunction with routine mammography). Other uses of breast
MRI include evaluation of response to neoadjuvant chemotherapy with
imaging before, during, and/or after treatment, and identification of residual
disease in patients with positive margins after lumpectomy.
Ultrasound
The current indications for breast ultrasonography include palpable
findings (including as the initial imaging test of palpable findings in patients
who are younger than 30 years, pregnant, or lactating), abnormalities or
suspected abnormalities on mammography or MRI, problems with breast
implants, suspected underlying mass in the setting of microcalcifications or
architectural distortion on mammography, supplemental screening in women
at high risk for breast cancer who are not candidates for or do not have easy
access to MRI, and suspected axillary lymphadenopathy. Real-time imaging
is also possible with ultrasonography, making it ideal for interventional
procedures Breast ultrasound imaging should be performed with a high-

31
 resolution real-time linear array transducer with a center frequency of at least
10 MHz, using the highest frequency with which adequate penetration of the
tissue is feasible.
Table 1. Breast imaging reporting and database system
Category Assesment Follow up
0 Need additional imaging Additional imaging needed before a
evaluation category can be assigned
1 Negative Continue annual screening mammograms
(women older than 40 yr)
2 Benign Continue annual screening mammograms
(women older than 40 yr)
3 Probably benign Initial short term follow-up (usually six
month) mammogram (< 2% chance of
malignancy
4 Suspicious abnormality Biopsy should be considered (2%-95%
chance of malignancy)
5 Highly suggestive of Requires biopsy (> 95% chance of
malignancy malignancy)
6 Known cancer Biopsy-proven malignancy
(American College of Radiology, 2003)

H. Screening

Screening with mammography every 2-3 years for women of average risk
(i.e. no family history, no BRCA mutations) from age 40-74 is associated with
reduced mortality. Women at increased risk of breast cancer should undergo
regular screening by imaging and breast examination at a younger age.
Screening with clinical breast examination or breast self-
examination is not associated with reduction in mortality.
Current Canadian guidelines recommend the following for women of average
risk

32
 No routine screening for women aged 40-49 due to high number of false
positives on mammogram and unnecessary biopsies compared to mortality
benefit.
 Routine mammography every 2-3 years for women aged 50-74 due to
mortality benefit outweighing false positive and unnecessary biopsy risk.
 Routine breast self-examination and clinical breast examinations are not
recommended.
 Discussion of this data with patients allows more autonomy for a personalized
screening schedule (CMAJ, 2011).

I. Treatment

1. Surgery

 Breast-conserving surgery (BSC): also known as lumpectomy or wide local

excision, BSC involves resection of the tumour along with a margin of tissue
while conserving the cosmetic appearance of the breast. Most breast surgeries
are of this type because (i) most tumours are locally invasive and (ii) large
primary tumours can be reduced in size by neoadjuvant chemotherapy prior to
conservative surgery.
 Mastectomy: surgical removal of entire breast, including the fascia over the
pectoralis muscles. Surgeons may preserve some skin and the nipple/areola
for reconstruction. The indication for mastectomy is multicentric invasive
carcinoma, inflammatory carcinoma, or extensive intraductal carcinomas.
 Axillary lymph node dissection: removal of the lymph nodes draining the
breast tissue for lymph node micrometastasis. This is done at the same time as
BSC or mastectomy. However, recent evidence suggests that axillary lymph
node biopsy is unnecessary regardless of whether the sentinel lymph node
biopsy is negative or positive because there is no mortality benefit.
 Adjuvant therapy: cytotoxic chemotherapy, endocrine therapy, or radiation
therapy may be used postsurgery to prevent relapse (Giordano, 2010)

33
2. Radiation therapy
Either whole or partial breast irradiation may be used
(see Carcinogenesischapter for mechanism of radiation therapy). Adjuvant
radiation therapy is applied post-BCS or post-mastectomy to prevent recurrence.
Since most recurrence of early-stage breast cancer occurs locally, partial
irradiation at the tumour site has similar mortality benefits as whole breast
irradiation. However, new evidence suggests an increased risk of local and
axillary recurrence with partial irradiation. Radiation of metastatic disease (e.g.
bone or brain metastases) is also used (Valachis, 2010).
3. Endocrine therapy
 Breast cancer is a hormone-sensitive cancer. Most breast cancer cells are ER-
positive, and thus will respond to reduction of circulating estrogens. HR-
negative breast cancers will not respond to endocrine therapy.
 Mainly used as (i) adjuvant therapy for early-stage hormone-sensitive breast
cancer or as (ii) first line therapy for metastatic hormone-sensitive breast
cancer.
 Cancer Care Ontario recommends 5 years of adjuvant endocrine therapy for
early-stage breast cancer in postmenopausal women.
 Antiestrogens (e.g. tamoxifen): Competitively binds ER and inhibits estrogen
binding.
 Aromatase inhibitors: Aromatase, also known as estrogen synthase, is an
enzyme responsible for estrogen synthesis. There are two types: steroidal
(type I) and non-steroidal (type II). The steroidal type (e.g. exemestane) is an
androgen analogue that binds permanently with the aromatase enzyme,
leading to long-term and specific inhibition of the enzyme. The non-steroidal
type (e.g. anastrozoleand letrozole) originates from an anti-epileptic drug that
reversibly binds and inhibits the cytochrome P450 unit in aromatase. Because
the non-steroidal type has a good molecular fit with the substrate-binding site,
it is more potent than the steroidal type. Both types have good efficacy and
high specificity for the aromatase enzyme.

34
 Ovarian ablation: induction of artificial menopause
by ovariectomy significantly reduces breast cancer
risk. Adrenalectomy eliminates a source of androgens in females, which is the
precursor to aromatase-derived estrogens. However, these surgical approaches
are irreversible and cause major side effects, so they are less often used.
 Ovarian suppression: LHRH (GnRH) agonist (e.g. goserelin and leuprorelin)
can be used to reversibly suppress LH/FSH release and thus estrogen release
(Miller, 2004)
4. Chemotherapy
Cytotoxic drugs, such as cyclophosphamide, methotrexate, doxorubicin, and
paclitaxel, are used in hormone receptor-negative or HER2-positive breast
cancers. They can either be given presurgery as neoadjuvant to shrink the tumour
or postsurgery as adjuvant to prevent relapse.

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