Breast cancer

1. Breast Cancer
By
Dr. Sheikh Abdullah al Mukit
Resident
Clinical Oncology, BSMMU

2. OUTLINE
• INTRODUCTION
• ANATOMY
• RISK FACTORS
• GENETIC MUTATION
• CLINICAL PRESENTATION
• INVESTIGATIONS
• TREATMENT
• PREVENTION

3. Introduction
What are breasts made of?
The different types of breast tissue include:
•Glandular: Also called lobules, glandular tissue produces milk.
•Fatty: This tissue determines breast size.
•Connective or fibrous: This tissue holds glandular and fatty
breast tissue in place.
What parts make up breast anatomy?
•Lobes: Each breast has between 15 to 20 lobes or sections.
•Glandular tissue (lobules): These small sections of tissue found
inside lobes have tiny bulblike glands at the end
•Milk (mammary) ducts: These small tubes, or ducts, carry milk
from glandular tissue (lobules) to nipples.
•Nipples: The nipple is in the center of the areola. Each nipple
has about nine milk ducts, as well as nerves.
•Areolae: Areolae have glands called Montgomery’s glands that
secrete a lubricating oil. This oil protects the nipple and skin
from chafing during breastfeeding.

4. Anatomy of the breast
Shape and position:
• conical in shape
• It extends from the sternal margin to the
mid axillary line at the level of 4th rib.
• Vertically, it extends from the 2nd rib to the
6th rib along the midclavicular line

6. Vascularization

7. Lymph nodes
1 -The anterior (pectoral) group
2-the posterior (subscapular)
group
3 – The apical group
4 central basal group
5 lateral (brachial) group

9. Breast Cancer
• Breast cancer is the most common life-
threatening cancer and the leading cause of
cancer mortality among women.
• It is the second most common cause of
death from cancer among women in the
world..

10. Epidemiology
• 1 in 8 women will be diagnosed in their lifetime.
• 1 in 1000 men will be diagnosed in their lifetime
(Primarily after the age of 60).
• In Bangladesh incidence rate of breast cancer
was about 22.5 per 100000 females.
• Breast cancer has been reported as the highest
prevalence rate (19.3 per 100,000) among
Bangladeshi women between 15 and 44 years of
age.
REF: Begum SA, Mahmud T, Rahman T, Zannat J, Khatun F, Nahar K, Towhida M, Joarder M, Harun A, Sharmin F.
Knowledge, Attitude and Practice of Bangladeshi Women towards Breast Cancer: A Cross Sectional Study. Mymensingh
Med J. 2019 Jan;28(1):96-104. PMID: 30755557.

13. Genetic mutations

14. Classic histopathologic classification:
- Ductal adenocarcinoma (70% to 80%)
- Lobular carcinoma (10% to 15%).
- Special breast cancer subtypes with a favorable
prognosis include papillary, tubular, mucinous, and pure
medullary carcinomas.
- Inflammatory breast cancer
- Paget disease of the breast,
- Cystosarcoma phyllodes (<1%)
- Rare tumors include squamous cell carcinoma,
lymphoma, and sarcoma.

16. Clinical Presentation
• LUMP is the commonest presentation. Spontaneous
nipple discharge is the Second most common sign
• 10% of patients present with nipple change.
• 5% of patients present with skin contour changes.
• Breast pain/mastalgia alone is a very uncommon
presentation.
• Ductal carcinoma may present as a bloody discharge
from the nipple.

19. Diagnosis
• HISTORY:
• Age: commonest between 45-65yr age –group
• Sex: 99-100 times commoner in females
• Painless, progressive breast swelling, most common
site being the upper outer quadrant of the breast.
• The swelling may be painful in inflammatory breast CA
• Ulceration of overlying skin, axillary swelling, upper
limb swelling (lymphedema)
• Blood-stained nipple discharge.
• Nipple changes: deviation, retraction, destruction

20. • History of Complications
• Metastasis
• CNS: headache, blurring of vision, altered consciousness,
vomiting
• Chest: cough, dyspnoea
• Abdomen: jaundice, ascites (abdominal distension)
• MSS: bone pains, weakness in limb, backache,
numbness/tingling sensation in lower limbs
• Fatigue due to anaemia

21. Physical examination
•General:
• Breasts: examine the normal breast before
the diseased breast
• Breast symmetry:
• Skin changes: peau d’orange (from blockage of dermal lymphatics),
Dimpling of skin due to infiltration of ligament of Cooper, Retraction of
nipple due to infiltration of lactiferous duct, Ulceration, discharge from the
nipple and areola, Skin ulceration and fungation, nipple changes
• A lump is palpable in the breast in about 50% of patients and in over 90% of
these there is a co-existing invasive cancer.
• When a lump is present, axillary nodes may be felt.

22. Physical examination
• CVS
• Abdomen
• Hepatomegaly and ascites from liver metastases.
• Rectal examination is done for pelvic metastases.
• Extremities and back
• The spine and skull are examined for tenderness or swelling.
• Neurological examination

24. inflammatory breast cancer

25. INVESTIGATIONS- BREAST USG:
• Useful to differentiate solid from cystic breast lesions.
• Useful in women < 35yrs with dense breast tissue. Sensitivity is 70-90%,
specificity is 80-95%. It is operator dependent.

26. MAMMOGRAPHY (Screen-film mammography-SFM)
• Useful after 30yrs of age when the breast tissue contains less dense
glandular tissue (but comprises more of fat)
• 10-15% of breast cancers are not seen on mammography
• Invasive breast cancer can look like a white patch or mass on a
mammogram. The tumor cells that began in the milk duct. The outer
edges of these cells look fuzzy or spiky (called speculated)

27. BI-RADS

28. MRI
 Useful for :
 the extent of multi focal or multicentric disease,
 for identifying primary foci in non-palpable lesions,
axillary metastases
 assessing response to neoadjuvant chemotherapy, for
recurrence in breast after surgery and/or radiotherapy
and also for screening high-risk and BRCA-positive
patients especially younger than 50 years.
 for detecting bone marrow metastases and
spinal cord compression.

30. CYTOLOGY:
• To determine if the lesion is benign or malignant.
• Can also distinguish ductal from lobular Cancer, though cannot
distinguish in-situ from invasive Cancer
• Yield increased by USG-guided FNAC or mammography-
guided FNAC

31. BIOPSY
Useful to make a definitive diagnosis of breast Cancer,
differentiates DCIS from invasive Cancer, determines
the histologic grade, level of differentiation and also in
determining the hormone receptor status (ER, PR and
Her-2/neu receptor status of the tumour. The BRCA 1
gene can also be done if indicated.
Biopsy technique:
1) needle biopsy
2) incisional biopsy
3) excisional biopsy

32. MOLECULAR SUBTYPE OF BREAST CANCER

33. Staging workup
• CXR: secondaries in the chest (canon-ball metastases, pleural
effusion or bony erosion).
• Abdominal USG: secondaries in the liver, ascites
• LFT: raised ALP may be due to metastasis to the liver
• SKELETAL SURVEY: Involve x -rays of the spine, pelvis and skull.
It is done to find the presence or otherwise of asymptomatic
osseous metastases.
• SKELETAL SCINTIGRAPHY: refers to bone scan using 87Sr or
18F. Picks up bony metastases 3- 6 months before they become
demonstrable by conventional X-ray.
• CT-scan of the brain: in suspected cranial metastasis
• PET/CT scan: if available, it is considered the most accurate
and useful imaging modality for staging metastatic breast
cancer because it provides whole-body assessment of soft
tissue, visceral and bony sites at a single examination.

34. Staging (pathological)

35. Staging-TNM

36. Grading of breast cancer

37. LOCAL INVASION:
Affects surrounding breast tissue, overlying skin, underlying
muscle, and chest wall.
• Occurs via:
• Direct infiltration into the surrounding parenchyma: - Macroscopic
stellate appearance
• Direct infiltration along the lactiferous duct: nipple retraction
• Involvement of the ligaments of cooper: dimpling of the skin
• Skin involvement leads to skin tethering (skin attachment), peau
d’orange (obstruction of dermal lymphatics), skin ulceration

38. Distant metastasis

39. TREATMENT
The Rx is multidisciplinary,
• Oncologists,
• Radiologists,
• Surgeons,
• pathologists,
• and other professionals
such as counsellors and
breast care nurses

40. Treatment modalities

41. Surgery
Breast-conserving surgery: Surgery to remove just the
cancerous lump (tumor).
• Lumpectomy:
• Partial mastectomy
• segmental mastectomy
Mastectomy: Surgery to remove the whole breast.
• Total (Simple) mastectomy
• Modified radical mastectomy
• Radical mastectomy

42. Chemotherapy
• They Antracycline based (CAF,CEF),
• Non-anthracycline(CMF) based
• Taxane based.

43. CHEMOTHERAPY

44. Chemotherapy

45. Chemotherapy

46. RADIOTHERAPY
• It reduces the incidence of loco-regional metastases in "early" breast
cancer,
INDICATIONS FOR RADIOTHERAPY
• After mastectomy in patients with high risk of loco-regional
recurrence
• Patients with 4 or more positive nodes
• Advanced primary tumour >5cm
• One invading the underlying muscle or adjacent skin
• Poorly differentiated tumour or one with lymphovascular invasion.
• Advanced metastatic carcinoma: Radiotherapy is beneficial for
alleviating bone pains and for controlling or treating the local
disease or recurrence

48. LINAC Machine in BSMMU

49. HORMONAL THERAPY
• If the tumour is ER +, hormonal therapy is given postoperatively.
• Indications for hormonal therapy
• Post-menopausal patients with ER + tumours with or without positive axillary
nodes.
Premenopausal patients may be similarly treated, but oophorectomy is
advised in developing countries.
• For palliation in patients with advanced ER+ carcinoma
• Preoperatively to shrink large ER + tumours and make them operable.
• During 3 months of tamoxifen, the tumour shrinks rapidly and there may not be any
evidence of tumour in the mastectomy specimen. The tumour shrinks by 25-50% in 2
weeks if 100mg is given daily.

50. • Drugs Used:
• Anti-oestrogens:
• Tamoxifen: better used in pre-menopausal women
• SAI (selective aromatase inhibitors): better used in post-menopausal women
• Reversible: Anastrozole/Arimidex
• Irreversible: Exemestane, Formestane
• Pure anti-oestrogens: Fulvestrant (Faslodex), given IM, once monthly. They are
steroids that bind oestrogen receptor and prevent oestrogen receptor dumerization
and DNA binding
• Progestins:
• Medroxyprogesterone acetate (500-1000mg/day)
• Megestrol acetate (80mg b.d)
HORMONAL THERAPY

51. • Targeted therapy
• Useful as an adjunct to other treatment modalities that reduce tumour burden.
• 20% of tumours express the human epidermal growth factor receptor gene (HER2/neu
gene). This receptor encodes a protein that accelerates the growth of metastatic breast
cancer.
• Trastuzumab is a recombinant monoclonal antibody against the HER2/neu gene.
• Pertuzumab
• Lapatinib inhibits the tyrosine kinase activity associated with two oncogenes, EGFR
(epidermal growth factor receptor) and HER2/neu (human EGFR type 2).
• Palbociclib, is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6.
• Everolimus

52. Immunotherapy
Pembrolizumab is a drug that targets PD-1 (a protein on
immune system T cells that normally helps keep them from
attacking other cells in the body). By blocking PD-1, these
drugs boost the immune response against breast cancer cells.
This can often shrink tumors.

53. FACTORS AFFECTING PROGNOSIS
• Lymphovascular involvement
• Presence or absence of axillary nodes: this is the most important prognostic index.
• Presence or absence of systemic dissemination.
• Histologic sub-type of tumour and grade of the tumour (different biologic
propensity):
• Intraductal mucinous, papillary, cribriform & tubular carcinomas have a slower
growth and better prognosis.
Medullary carcinoma with lymphocytic infiltration also has a good
prognosis. (pure variant of medullary has poor prognosis)
• Invasive ductal CA Nos (not otherwise specified) is the commonest form of invasive
ductal Cancer. It has an intermediate prognosis
• Some rare forms of breast cancer (e.g. sarcomatoid carcinoma, inflammatory
carcinoma) have a poor prognosis..

54. • Size of the tumour at the time of diagnosis: small tumours have a
better prognosis than big tumours. Tumours < 1cm are unlikely to
metastasize
• Hormone receptor status: tumours with oestrogen receptors have a
best prognosis within the first 5 years and over than those without.
They have > 70% response rate to hormonal therapy
• Over-expression of oncogenes such as HER-2/neu gene:
Good prognosis.(But only if targeted therapy given).
• Tripple Negative Breast Cancer: Worst prognosis
• Menstrual status of the patient: pre-menopausal patients do better
than post-menopausal patients. Women between 35 and 49 have on
the whole a better prognosis than those over 50yrs or less than 35.
• Age & Sex

55. SCREENING FOR BREAST CANCER
• Self breast examination: done on 7th-10th days of the cycle, in
supine position.

56. • Women ages 40 to 44 should have the choice to start annual
breast cancer screening with mammograms if they wish to do so.
• Women age 45 to 54 should get mammograms every year.
• Women age 55 and older should switch to mammograms every 2
years.
• Indications
• Women > 50yrs
• Patients who have had breast conservation for breast CA. Both breasts
should be screened
• Those who have had mastectomy.
• Strong family History.(starts screening in 30-35 years)
• Detects small lesions, sometimes not yet palpable. These are
biopsied.
Mammography

57. • Suspicious features include:
• Stellate or irregular densities
• Altered breast architecture
• Micro-calcification (> 2mm), which may be clustered, punctate,
microlinear or branching and concentrated in an area > 1cm in
diameter.
•Disadvantages/limitations
• 10-15% of cancers are not detected by mammography. Cancer may also occur
in-between screening (interval carcinoma).
• Difficult to detect lobular carcinoma, because of minimal calcification

58. Prevention

60. BREAST CANCER PREVENTION
1. Early detection and treatment; screening and surveillance
2. Chemoprevention
• Tamoxifen; recommended only for women who have a Gail relative risk of 1.66% or
higher, who are aged 35 to 59, women over the age of 60 or women with a diagnosis
of LCIS or atypical ductal or lobular hyperplasia. When taken for 4-5 years, it reduces
the incidence of invasive breast cancer
• Aromatase inhibitors (AIs); have been shown to be more effective than tamoxifen in
reducing the incidence of contralateral breast cancers in postmenopausal women
receiving AIs for adjuvant treatment of invasive breast cancer.
3. Risk reducing surgeries
• Prophylactic bilateral mastectomy: recommended for BRCA 1 and 2 mutation carriers
and other high-risk patients after genetic counselling. It reduces breast cancer risk by
90%.
• Prophylactic bilateral oophorectomy (in premenopausal women): reduces risk by
50%.

62. Take home message