This document summarizes the anatomy, pathology, and epidemiology of breast cancer. It discusses the embryology, gross anatomy, histology, and molecular classification of the breast. It also describes the epidemiology of breast cancer, noting key risk factors like family history, age, reproductive history, hormone exposure, radiation exposure, BMI, physical activity, and diet. Screening and management of breast cancer is available at various levels of healthcare centers in India.

1. BREAST
ANATOMY PATHOLOGY EPIDEMIOLOGY

2. REVISION OF
• EMBRYOLOGY
• PHYSIOLOGY
• GROSS ANATOMY
• HISTOLOGY
• HISTOPATHOLOGY
• EPIDEMIOLOGY
• RADIOLOGY

3. EMBRYOLOGY
STARTS FROM 4TH WEEK OF INTRA
UTERINE LIFE
MAMMARY RIDGE > MAMMARY PIT>
SECONDARY BUDS (LOBES)
GLAND FROM ENDODERM
STROMA FROM MESODERM
NIPPLE DEVELOP AT THE PLACE OF
MAMMARY RIDGE

4. CLINICAL
SIGNIFICANCE
LINE OF SCHULTZ
POLYTHELIA
POLY MASTIA
ATHELIA
AMASTIA
DIFFUSE HYPERPLASIA

5. BREAST
MODIFIED SWEAT GLAND
NO SPECIAL CAPSULE OR SHEATH
PRESENT IN BOTH SEX
IN ANIMALS ,GENUS MAMMALS IS MARKED BY
THE PRESENCE OF THESE GLANDS
SECONDARY SEX ORGAN
ORGAN OF LACTATION

6. DIVISION
• BREAST IS DIVIDED INTO 5 QUADRANTS FOR EASY AND
UNIFORM REPORTINGOF LUMP LOCATION
• THE BREAST EXTENDS TOWARDS AXILLA AND CALLED TAIl
OF SPENCE
• IN SOME PEOPLE IT IS USUALLY PALPABLE , IN SOME
DURING PREMENSTRUAL PHASE AND LACTATION
• hence the upper outer quadrant has more tissue than others and
so greater incidence of cancer (38.5%)
• CENTRAL AREA 29% UIQ 14.2% LOQ 8.5% LIQ5%
• there is a pattern of drainage from each quadrant, for eg. upper
outer quadrant more to axillary nodes

7. GROSS ANATOMY
• EXTENSION
• 2nd rib to 6/7 th rib
• lateral border of sternum
• mid axillary line
• MAY ALSO EXTEND
• clavicle to 8th rib
• midline
• upto lattismus dorsi
significance ; during mastectomy
whole breast has to be removed

8. BREAST BED
• medially 2/3 rd by pectoral fascia overlying
pectoralis major
– between investing breast fascia and
pectoral fascia there is aspace
containing loose areolar tissue ,due to
this the breast is mobile over P.M
muscle.in optimally taken
mammography this space is visible
• rest by fascia over serratus anterior
• inferiorly external oblique aponeurosis
• for staging chest wall is formed by
serratus anterior , ribs and intercostal
muscles (perez)

10. WITHIN
• GLAND PARENCHYMA :
– NIPPLE > LACTIFEROUS SINUS > DUCT > LOBE >
EXTRA LOBULAR TERMINAL DUCT > LOBULE >
INTRA LOBULAR TERMINAL DUCT > ACINI
– during pregnancy the acini will proliferate and lobule
becomes store house of milk , stroma will be less
• STROMA :
– INTERINTERLOBULAR & INTRA LOBULAR
• TDLU - TERMINAL DUCTAL LOBULAR UNIT functional
unit of breast with 30 -50 acini (1-4 mm) ,
• Origin of cancer - TDLU

11. NIPPLE AND AREOLA
• Nipple where then lactiferous duct ends
and milk is ejected out and
circumferential skin sdevoid of fat, hair
and sweat glands the areola, contains
smooth muscle arranged concentrically
thus erectile in nature.
• retraction of nipple :
– congenital - can be everted
– acquired ( cannot br everted )
– slit like - duct ectasia
– circumferential - carcinoma infilterating
ducts
– hence in carcinoma nipple areolar
complex is distorted
– it is not considered as skin involvement

12. discharge from nipple
• milk - lactation , new born
babies ( physiological),
prolactinemia pituatory
adenoma, bronchogenic
ca
• green - duct ectasia
• bloody - carcinoma,
• pus- mastits, abscess

13. coopers ligament
• condensed fibrous
connective tissue attached
from superficialascia to
dermis of skin overlying
breast
• supportive structure
• infilteration of skin by
carcinoma causes
dimpling/puckering of skin
• it is not considered as
skin involvement in staging

14. ARTERIAL
SUPPLY
• subclavian artery > internal
thoracic artery
• axillary artery> lateral thoracic
, superior thoracic , acromio
thoracic
• posterior interscostal artery
lateral branch
• anterior part of breast
receives more blood supply
and posterior part relatively
avascular

15. VENOUS
DRAINAGE
• superficial veins - internal
thoracic vein, superficial
veins in lower part of neck
• deep veins - axillary and
posterior intercostal veins

16. en route spine -THE BATSON’S
PLEXUS
• a network of valveless veins in the human body
that connects the deep pelvic vein and thoracic
veins to internal vertebral venous plexus
• invests the vertebra and extends from base of
skull to sacrum
• posterior intercostal veins> azygous
/hemiazygous veins along side the body of
vertebrae > batson vertebral venous plexus >
internal vertebral venous plexus surrounding the
spinal scord

18. NERVE SUPPLY
• medial and lateral
thoracic intercostal
nerves
• supraclavicular nerves

19. AXILLA

20. IC
DRAINAG
E
• NIPPLE AREOLA
&LOBULES , INTER
LOBULAR
CONNECTIVE
TISSUE >
SUBAREOLAR
LYMPHATIC PLEXUS
> NODES
• SKIN (EXCLUDING
NIPPLE AND AREOLA
) > AXILLARY AND

22. PEAU D’ ORANGE
• Due to blockage of
subareolar lymphatic
plexus by metastatic cells
(lymphedema)
• In turn causes deviation of
nipple and thickened
leather-like appearance of
skin
• Prominent or puffy skin
between dimpled pores →
orange peel appearance

23. LEVEL WITH
RESPECT TO
PECTORALIS
MINOR BERG”S
GROUP AXILLARY FOSSA RELATION TO ADJACENT
STRUCTURE
NUMBER OF
NODES
Level I Lymph
nodes (lateral or
below the lower
border of Pectoralis
minor
Axillary vein group
(Humeral group)
lateral Medial or posterior to axillary
vein
4-6
External mammary
group
anterior or pectoral Along lower border of pectoralis
minor Contiguous with lateral
thoracic vessels
5-6
Scapular group posterior or
subscapular
Along posterior wall axilla at
lateral border of scapula
Contiguous with subscapular
vessels
5-7
Level II Lymph
nodes (superficial
or deep to
pectoralis minor)
Central group central Embedded in fat
Immediately posterior to
pectoralis minor
3-4 sets
interpectoral group
(rotters node)
Interposed between pectoralis
major and pectoralis minor
1-4
Level III Lymph
nodes (medial or
above the upper
border of pectoralis
minor
Subclavicular group apical Posterior and superior to upper
border of pectoralis minor
6-12 sets

24. INTERNAL MAMMARY
NODE
Lymph vessels that accompany the perforating
branches of internal mammary artery enters
into para sternal (internal mammary) nodes
Lie along the int.mam vessels, deep to the
plane of costal cartilage
Not routinely dissected although once they
were biopsied for staging
Drains into broncho mediastinal trunk

26. PATHWAY OF
SPREAD
• Diagrammatic representation of lymphatic drainage (single
line) and blood spread (double line) in carcinoma of the breast.
• Lymphatic drainage from the subareolar plexus of Sappey and
outer quadrant of the breast takes place first to the pectoral (P),
then central (C) and lastly to the apical (A) group of axillary
lymph nodes.
• The other two groups of the axillary nodes, viz. the subscapular
and lateral group may be involved in a retrograde way. From
the apical group the supraclavicular group may be affected.
• On the left side the supraclavicular group is affected by
retrograde permeation.
• The upper quadrant of the breast drains partly to the delto-
pectoral node but mainly to the apical group. From the inner
quadrant the lymph spread occurs to the internal mammary
group (In. M) and to the other breast (Br).

27. • From the lower and inner
parts of the breast the lymph
vessels form a plexus over
the rectus sheath and pierce
the costal margin to
communicate with the
subperitoneal lymph plexus.
• From this place, cancer cells
may drop by gravity into the
pelvis (Transcoelomic
implantation) and may cause
metastases in the ovary
(Krukenberg's tumour).
• It may be noted that the liver
may be involved in two ways
subperitoneal plexus and by
blood spread.
• Blood spread - occurs in

28. • Axillary nodes → clavicular (infra and
supraclavicular) lymph nodes → subclavian
lymphatic trunk (drains upper limb)
• Parasternal lymph nodes →
bronchomediastinal trunk (drains thoracic
viscera)

29. HISTOLOGY

31. HISTOPATHOLOGY

32. • histologically
• non invasive lesions
• invasive lesions

33. NON INVASIVE
PAGETS DISEASE
DCIS
LCIS

34. DCIS
It is confined to the ductal system of the breast
It lacks the histologic evidence of invasion
From low grade non –comedo DCIS to high grade comedo DCIS
• Comedo
• Solid
• Cribriform
• Micropapillary
• Papillary
Based on the architectural or morphological appearance:

35. Comedo
1.Comedo solid Micropapillary
DCIS
Cribriform
Papillary DCIS

36. Growth pattern
Unicentric – one area only
Multicentric – two different areas separated by >4cm
Continuous - extension along ductal systems without gap
Multifocal/ discontinuous - two or more areas separated by <4cm

37. LCIS
• It is a benign entity
• Loose discohesive epithelial
cells that are large in size
,variable in shape and normal
cytoplasm to nuclear ratio.
• ER –positive
• Loss of e-cadherin
• Represents <15% of all non-
invasive breast ca

38. PAGETS DISEASE
CRUSTING AND ECZEMATOUS CHANGES OF
NIPPLE AND AREOLAR COMPLEX
PRESENCE OF PAGETS CELLS THROUGHT
THE EPIDERMIS
MOSTLY ASSOCIATED WITH UNDERLYING
MALIGNANCY
SO COMPLETE EXAMINATION OF THE
BREAST IS IMPORTANT
ECZEMA IS B/L but PAGETS DISEASE IS U/L

39. INVASIVE LESIONS OF THE BREAST
• invasive carcinoma of no special type
• invasive carcinoma special types
– ductal
– tubular
– mucinous
– medullary
– inflammatory
– lobular

40. • sarcoma
• neuro endocrine tumors

41. molecular classification of breast cancer

44. ER
• estrogen receptor gets
activated and leads to cell
proliferation
• ER is positive about 70%
breast ca
• er are mostly nuclear
receptor, and central part
of the cell gets stained

47. ALL RED SCORE
About 70% breast cancers
are ER positive cancers

48. Her 2 algorithm

49. HER 2

50. Her 2 positive

51. BREAST CANCER
• MOST COMMON CANCER among WOMEN
WORLDWIDE
• THE OLDEST EVIDENCE OF BREAST CANCER IS
4200 years ago IN EGYPT
• CAUSE OF BREAST CANCER – CUMULATIVE
EFFECT OF GENETIC, ENVIRONMENTAL,
HORMONAL, LIFESTYLE FACTORS
• SCREENING, MANAGEMENT IS EASILY AVAILABLE
AT NCD CENTRES FROM SUBCENTRE LEVEL TO
RCC

52. EPIDEMIOLOGY OF BREAST
CANCER
AGE
• incidence of breast cancer increases exponentially upto menopause , then slowly
, after 80 th rate slowly declines
Age at first child birth
• Mac mahon et all : linear relation between age at first child birth and incidence of
breast cancer
• Aged 20 – 25 at first child birth have 50% decreased risk than nulliparous women
• Breast feeding _ no sufficient data
SEX females > males

53. Ovarian function
• Long menstrual history ,
early menarche and late
menopause _ long
estrogen exposure
Exogenous hormone
• Increased RR of 1.35 for
current or recent users of
hormonal replacement
• Post menopausal hormone
therapy RR increase by
2.3% foe each year
The use of oral contraceptive
pill has not been consistently
shown to increase the risk of
breast can cancer

54. • Family history
– 1st degree relative (mother or sister) risk is 1.7 to 2.5
– 2nd degree relative (grand ma or aunt ) risk is 1.5
• Due to mutation In BRCA 1 , BRCA 2 , shared life style , inheritance of genes for other risk
factors ( body habitus , age at menarche)
• Although mutation is present in 1% of population and approx. 5 to 10%breast cancer cases
, women with mutation carry lifetime risk of 70% to 80% .

55. NCCN guidelines for genetic testing
1. The individual has a family history of a known BRCA1/BRCA2 mutation
2. Personal history of breast cancer plus one of the following:
a. Diagnosed age 45 years or younger
b. Diagnosed age ≤50 years with one or more close blood relatives with breast cancer at
any age, one or more close blood relatives with pancreatic cancer, one or more close
blood relatives with prostate cancer, or an unknown or limited family history. Diagnosed
age ≤60 years with a triple negative (TN) breast cancer. Diagnosed at any age with two
or more close blood relatives with breast, pancreatic, or prostate cancer at any age, ≥1
close blood relative with breast cancer ≥50 years, ≥1 close blood relative with ovarian
cancer, close male blood relative with breast cancer or an individual of ethnicity
associated with higher mutation frequency (e.g., Ashkenazi Jewish). Personal history of
epithelial ovarian/fallopian tube/primary peritoneal cancer, or
c. c. Personal history of male breast cancer

56. • Personal history of breast cancer and history of benign breast biopsy
– Patients treated for invasive breast cancer or DCIS have similar risks of
developing a contralateral breast cancer, which does not appear to be
effected by the type of local therapy for the initial lesion
– recent analysis of the SEER database demonstrated that 4.2% of localized
invasive or intraductal breast cancer patients surviving at least 3 months
developed contralateral breast cancer with the 10- and 20-year actuarial rate
of CBC being 6.1% and 12% .

57. • Prior radiation exposure
– Land et al.26,27 reviewed reports on three populations of
patients exposed to ionizing radiation by atomic bombings,
multiple fluoroscopic examinations for tuberculosis, and
multiple examinations for mastitis. They concluded that the risk
of radiation-induced cancer of the breast increased
approximately linearly with increasing dose and was heavily
dependent on age at exposure.
– 28 A high risk of solid tumors, especially breast cancer, has
been described in
women treated with RT at a young age for Hodgkin lymphoma

58. • BMI
– The higher risk of breast cancer with
increased BMI in postmenopausal
women is likely due to higher
estradiol levels associated with
increased adipose tissue and
increased aromatase, which is
involved in the conversion of
androgens to estradiol

59. • Physical activity and diet
– A majority of studies, however, have observed a lower risk of
breast cancer among women who are more physically active
compared with women who are sedentary
– large prospective studies have failed to demonstrate an
association between dietary fiber intake and breast cancer risk.
• Assessing the individuals risk
– In the Gail model, an individual’s annual risk of breast cancer is
based on her present age, number of first-degree relatives with
breast cancer, age at first birth, age at menarche, number of
breast biopsies, and history of atypical ductal hyperplasia. The
use of exogenous hormones is not considered in this model,
and many of the other risk factors discussed above are not

60. GENETIC MUTATION
• All forms of breast cancer are believed to develop as a
consequence of
unregulated growth, and development of phenotypic
changes – ability to invade , angiogenesis, metastasize
• These changes in phenotypes are secondary to aberrations in
genetic pathways
– Few aberrations are inherited( germ line mutation)
– Others develop during the life of breast cell ( somatic mutation)

61. Germline muation
1. the p53 tumor suppressor gene – guardian of genome
, direct response to DNA injury
2. Muation – childhood sarcoma, gynaec ca, breast ca
3. Li – Fraumeni syndrome – 90% life time risk of
developing breast ca
• BReast CAncer gene BRCA 1 and BRCA2 tumor
suppressor gene , mediating cellular response to DNA
injury
• Germline mutation inBRCA 1 and BRCA 2 are rare ,

63. BRCA1
• CHROMOSOME 17
• Breast Cancer:
-Path: Often "Triple Negative" (ER/PR/Her2-),
- YOUNGER Age
Ovarian Cancer:
• - HIGHER Risk: up to -50-60% - YOUNGER Age of
onset
• Other Cancers:
• - Pancreas: -3-4%
• - Prostate: increased
• - Male Breast: increased
• - Colon??
– hboc
BRCA2
• CHROMOSOME 13
• Breast Cancer:
• -Path: Similar to Sporadic (ER/PR+, Her2-)
• -Slightly OLDER than BRCA1
• Ovarian Cancer:
• - LOWER Risk: up to -27% - OLDER Age (usually >
age 50)
• Other Cancers:
• - Pancreas: up to 10%
• - Prostate: HIGHER than BRCA1
• - Male Breast: 6-7%
• - Stomach, Gallbladder/Bile Duct,
• Melanoma

65. The NCCN has published a guideline
recommending that individuals with a genetic
predisposition
• undergo breast awareness starting at age 18,
• annual clinical and self-breast examination starting at age 25,
• annual mammography or magnetic resonance imaging (MRI)
• semiannual clinical and self-breast examination after age 25.
• In addition, annual pelvic examinations with transvaginal sonography, color
Doppler examinations of the ovaries, and measurement of serum(CA- 125)
levels can be considered beginning at age 30 to 35 years.
• For those women aged 35 to 40, a risk-reducing bilateral salpingo-
oophorectomy is recommended, with possible short-term hormone
replacement therapy.

66. ultrasonogram

67. mammogram

68. Tomosynthesis

69. CT
ANATOMY

73. MRI

75. TAKE HOME MESSAGE
• Breast is present in both sex
• upper outer quadrant has more tissue than others and so
greater incidence of cancer (38.5%)
• for staging chest wall is formed by serratus anterior , ribs
and intercostal muscles (perez)
• Dimpling of skin, nipple retraction, peau d orange app are
not skin involvement
• TDLU - TERMINAL DUCTAL LOBULAR UNIT functional
unit of breast
• LCIS - is not included in TNM staging
• focality and centric is said using intervening normal tissue
not by the quadrant involved

76. • lymphatic drainage is IMN along
with ALN
• in cause - exogenous estrogen
;only the post menopausal
hormonal therapy but not the ocp
• hereditary cause of breast cancer is
only 5 to 10 % , somatic acquired
muation is more common
• it is the cumulative effect of many
factors that leads to cancer
• positive in cancer : ER - 70 % ,Her
2 - 15 to 20%

77. Reference
• ANATOMY
– BD CHAURASIA 6TH EDI
– NETTERS ATLAS 5TH EDI
• EMBRYOLOGY
– INDERBIR SINGH 1OTH EDI
• HISTOPATHOLOGY
– ROBBINS 9TH EDI
• EPIDEMILOGY
– PEREZ 7TH EDI
• IMAGING ANATOMY
– Radiopedia.com

78. ACKNOWLEDGEM
ENT
Prepared by
PG - G K Pragatheeswari
Assistant Profeesor – Dr. Poongodi
Professor- Dr. Jeeva