Based on the WHO statistics and NCCN guidelines this power point is a current update on the management of breast cancer.

1. BREAST CANCER
UPDATE ON MANAGEMENT
DR. M. YIGAH

4. EPIDEMIOLOGY
Breast carcinoma is the most burdensome malignancy in
women globally
◦ Accounts for 26.7% of all prevailing malignancies in women.
◦ Leading cause of cancer deaths in women
Geographical variation of the incidence of breast cancer
◦ Higher incidence in developed nation than less developed
nations (except Japan)
◦ Increasing trend in less developed nation as they adopt
Western lifestyle.

5. A Study On Breast Ca In KBTH: Assessing The Impact
Of Health Education’.
◦ The majority of the Patient presents in the fifth decade
(40 - 49) – 40%
◦ Most women presents with advanced disease (stage 3&4) –
57.6%
◦ They also identified a high rate of defaults among
Patients
(Clegg-lamptey and Hodasi 2007)
Breast Cancer Treatment and Outcomes at Cape Coast
Teaching Hospital
◦ Ghanaian women frequently present with advanced stage
breast cancer and experience poor outcomes

6. BCS
15
29%
MASTECTOMY
37
71%
MALIGNANT BREAST SURGERIES
BCS
MASTECTOMY
STATISTICS OF SURGERIES DONE
FOR MALIGNANT BREAST DISEASE
IN CCTH FROM JAN 2017 – OCT
2020

7. PATHOLOGY TEAM
Averagely 125 cases are diagnosed per year
for the past 3 years
Total of 375 cases over 3 years

8. • Accessory Reproductive Organ
• Bed of the breast
• Axillary process
• Retromammary space
• Parenchyma and Stromal tissues
• Lobules, lactiferous ducts and sinuses
• Fatty matrix, fibrous tissues
ANATOMY

9. VASCULAR SUPPLY

10. VENOUS DRAINAGE

11. LYMPHATIC
DRAINAGE

12. RISK FACTORS FOR BREAST
CANCERS
1.Age
◦ 75% of women with breast cancer > 50 years in
Caucassians
◦ Younger age distribution in Africans
2.Gender
3.Geographic factors
◦ Higher in the Americas and Europe than in Asia and Africa.
◦ Migrants from low incident countries acquire incident rate of host
nation

13. RISK FACTORS FOR BREAST
CANCERS
4. Race/Ethnicity
◦ European descent - high incidence but less aggressive
tumours
◦ Hispanic and African American – more aggressive tumor at
younger age (40 – 49)
5. Family History (Genetic factors)
◦ Multiple affected first-degree relatives with breast cancer
◦ Inheritance of mutated BRCA-1 (risk 65 – 85%) or BCRA-2 genes (risk
- 40-85 %)

14. RISK FACTORS FOR BREAST
CANCERS
1.Reproductive History
◦ Early menarche
◦ Nulliparity
◦ Older age at first pregnancy
◦ Absence of breastfeeding
◦ Oestrogen containing contraceptives and HRT
2. History of breast cancer
3. Irradiation
4. Other risk factors - Fatty diet, Alcoholism, Smoking

15. HISTOPATHOLOGY
Noninvasive
◦ Ductal carcinoma in situ
◦ Lobular carcinoma in situ
Invasive
◦ Invasive ductal carcinoma 70% to 80%
◦ Invasive lobular carcinoma — 10% to 15%
◦ Carcinoma with medullary features— 5%
◦ Mucinous carcinoma (colloid carcinoma) — 5%
◦ Tubular carcinoma -- 5%
◦ Other type

16. Ductal Carcinoma In-situ
Lobular Carcinoma In-situ

17. Invasive Lobular Carcinoma
Invasive Ductal Carcinoma

18. MOLECULAR SUBTYPES OF TUMORS

19. PERCULIARITY OF BREAST CANCER
IN AFRICA
1. Younger age distribution (Othieno-Abinya 2000; Amir et
al, 2000)
◦ Kenya – median age is 44
◦ Tanzania – median age is 44.7
2. Tumors tend to be large > 2cm
3. Many of the tumors are hormone receptor negative
◦ ER negativity – (36 to 79%) & PR negativity -- (30–
87%)
4. Many of the tumors are triple negative breast
cancer (poor prognosis)

20. CLINICAL FEATURES
◦ Asymptomatic (Incidental finding)
◦ Painless swelling in the breast
▪ Persistent hard, discrete and fixed lumps
▪ Skin changes - Peau d’orange, nodules and
ulcerations
▪ Nipple retraction, Paget 's disease or Bloody
discharge
▪ Axillary swelling
▪ Lymphoedema of the arm or breasts

21. CLINICAL FEATURES
◦Features of metastasis
▪ Lungs and pleura – cough, dyspnoea,
▪ Bone – bone pain, pathological fractures
▪ Paraplegia – cord compression
▪ Liver - hepatomegaly and ascites
▪ Brain - headaches, vomiting, altered
consciousness or localizing signs.

22. TRIPLE ASSESSMENT
IMAGING
Mammography
◦ Diagnostic and
Interventional Purposes
◦ Requested for patients >
35 years
◦ [Sensitivity of 77 - 95%]

23. TRIPLE ASSESSMENT
IMAGING
Indications for Mammography
a.Routine breast screening
b.Assess a breast lesion detected after clinical
examination
c.Elderly patient with complaints – lumps, pain
d.Ruling out malignancy in the contralateral
breast
e.Assessing for multicentricity and multifocality
as part of work up for BCT
f.Follow up after treatment for breast cancer

24. Normal Post Menopausal Breast
Mediolateral Oblique
View (MLO)
Cranio-caudal
View (CC)

25. Normal of a Young Woman
Mediolateral Oblique
View (MLO)
Cranio-caudal
View (CC)

26. A Post-Menopausal woman with
Breast Cancer
Mediolateral Oblique
View (MLO)
Cranio-caudal
View (CC)

27. TRIPLE ASSESSMENT
IMAGING
Ultrasonography
◦ Useful in patient with dense glandular tissues (<
35yrs)
◦ Can be used as adjunct to mammography
◦ Can be used to guide biopsy
◦ To assess regional lymph nodes

28. TRIPLE ASSESSMENT
IMAGING
MRI
◦ Extent of multifocality or multicentricity.
◦ Identifying primary foci in nonpalpable lesions
◦ Axillary metastases apparently without a primary focus
◦ Assessing response to neoadjuvant chemotherapy,
◦ Assessing recurrence in breast after surgery and/or
radiotherapy,
◦ Screening high-risk and BRCA positive patients especially
younger than 50 years.
◦ It is also useful for detecting distant metastasis

29. TUMOR IN THE CONTRALATERAL BREAST MULTIFOCAL & MULTICENTRIC BREAST
CANCER
MRI

30. TRIPLE ASSESSMENT
HISTOLOGICAL ASSESSMENT
Sampling of tissues
◦ Core biopsy is preferred to FNAC and Open biopsies
◦ FNAC can not be used to differentiate between invasive
carcinoma
◦ Open biopsies - Paget's disease, ulcerated tumour and in
inflammatory breast cancer
Reducing Sampling errors
◦ Image guided biopsies – USG and mammogram
◦ Wire localization – especially for impalpable lesions

31. STAGING INVESTIGATIONS
Assessing for metastasis to the chest, abdomen and pelvis
◦ CT Scan of the Chest, Abdomen and Pelvis – Recommended
modalities
◦ Chest Xray & Abdominopelvic Scan - When CT Scan is not
available
Assessing for metastasis to the bones
◦ Bone scintigraphy – Detects bony metastases 3-6 months
before X-ray
◦ Skeletal survey – Conventional X-ray of the skull,
vertebrae and the pelvis.
Assessing for Brain metastasis – CT Scan

32. 8th Edition of the AJCC Breast
Cancer Staging
◦ Anatomic staging (TNM Staging) -
◦ Clinical staging
◦ Pathological staging
◦ Post-neoadjuvant therapy staging
◦ Restaging
◦ Prognostic staging
◦ Tumor grade,
◦ Hormone receptors and oncogene expression
◦ Multigene testing

33. Anatomic Staging –
Primary Tumour

34. Anatomic Staging – Regional
Lymph Nodes

35. Anatomic Staging –
Distant Metastasis

36. Anatomic
Group
Staging

37. PROGNOSTIC
STAGING
1. Tumor Grade
2. ER, PR, and HER2 Expression
3. Gene Expression Profiling
◦ Luminal A, Luminal B,
◦ HER2-enriched basal-like tumors,
◦ Basal-like
◦ Triple-negative non-basal tumors
4. Multigene Panels
◦ Oncotype DX Breast Recurrence Score

38. STAGE MIGRATION

39. TREATMENT MODALITIES
1. Loco-regional treatment
a. Surgery
b. Radiotherapy
2. Systemic treatment
a. Cytotoxic Chemotherapy
b. Hormonal therapy
c. Monoclonal antibodies for HER -2

40. SURGICAL LOCO-REGIONAL
TREATMENT
1. Breast Conservation Therapy - Wide local
Excision
◦ Lumpectomy
◦ Quadrantectomy
◦ Tylectomy
◦ Segmental mastectomy
2. Total Mastectomy

41. CANDIDATES FOR BCT
1.Impalpable breast tumours
2.Stage I or II invasive breast cancer.
3.Tumors with good response after neo-adjuvant
chemotherapy

42. CONTRAINDICATIONS FOR BCT
1.Absolute Contraindications
◦ Inability to have radiotherapy – pregnant women, lack of
facilities
◦ Diffuse malignant appearing micro-calcification on
Mammogram
◦ Multicentric breast tumor
2. Relative Contraindications
◦ Previous radiotherapy to breast or chest wall
◦ Persistently positive margin
◦ Suspected genetic predisposition to breast cancer
◦ Tumours > 5cm
◦ Small breasts

43. COMPONENTS OF BCT
1.Wide Local Excision
2.Axillary Node Clearance
◦ Sentinel lymph node biopsy followed by clearance
1.Radiotherapy
2.Oncoplasty

44. UPDATE ON SUGICAL MARGINS
◦Current consensus on clear surgical margin
“no ink on tumor.”
◦ Wider margins beyond the point of no ink on tumor did not
further reduce the risk of ipsilateral recurrence.
◦ (Int. J. Radiation Oncol. Biol. Phys. 2014;88:553-
64).
◦Intraoperative frozen section is increasingly
available and improves surgical outcomes

45. BCT vs Total Mastectomy
Six prospective randomized trials have shown that
overall and disease-free survival rates are similar
with BCT and mastectomy.
Data from the EBCTCG meta-analysis revealed that the
addition of radiation reduces recurrence by half and
improves survival at year 15 by about a sixth.
BCT is now oncologically equivalent to
mastectomy

46. SURGICAL LOCO-REGIONAL
TREATMENT
1.Total Mastectomy with Axillary Clearance
◦ The breast and axillary lymph nodes and fat are removed en-bloc
◦ Axillary clearance is indicated as per new NCCN guidelines.
◦ Can be followed immediately by oncoplastic
surgery (Improves compliance)

47. Skin Sparing Mastectomy

48. Case for Bilateral
Mastectomy for Unilateral
Breast Cancer
Analysis of women included in the SEER
database treated with mastectomy for
contralateral mastectomy performed at
the time of treatment of a unilateral
cancer was associated with a reduction
in breast cancer-specific mortality only
in the population of young women (18 –
49yrs) with stage I/II ER-Negative
Breast Cancer

49. NCCN Guidelines for Surgical
Axillary Staging
For clinically positive lymph nodes
1. There must be pathologic confirmation before ALND
2. Level I and II ALND is limited to patients with biopsy-
proven metastasis
3. Level III ALND should be done only if there is gross
disease apparent in level I and II
4. At least 10 lymph nodes must be provided for accurate
pathologic evaluation

50. NCCN Guidelines for Surgical
Axillary Staging
For clinically negative nodes or if core biopsy of
suspicious node is negative
1. Sentinel Lymph Node Mapping is done
2. For Breast Ca stage I/II with no preop treatment but due to
have adjuvant radiotherapy there is no need for ALND.
3. If any of the above criteria are not met, then level I and
II axillary lymph node clearance
4. Axillary radiation can replace ALND for patients undergoing
Mastectomy with Positive SLN

51. RADIOTHERAPY
Indications
1. As part of BCT for invasive carcinoma
2. High risk of locoregional recurrence after mastectomy
a. Advanced primary tumour (i.e., a tumour > 5cm)
b. Positive margins
c. Invading the underlying muscle or adjacent skin
d. Poorly differentiated tumour
e. Lymphovascular invasion
3. To control symptoms of locally-advanced cancer
4. Advanced metastatic carcinoma

52. RADIOTHERAPY IN ELDERLY
PATIENTS
In the PRIME II (a randomized controlled
trial)
◦ Women ≥ 65 years receiving endocrine therapy following
lumpectomy of low-risk tumour grade without positive lymph
nodes did not require radiotherapy.
◦ Local recurrence rate was higher but overall survival rate
was not significant
Radiation therapy may be avoided in selected
older patients with low-risk tumors.

53. SYSTEMIC TREATMENT
◦ General Treatment Regimen
◦ Cytotoxic Chemotherapy
◦ +/- Targeted Therapy
◦ +/- Hormonal Therapy
◦ Neo-adjuvant therapy or Adjuvant therapy
◦ Randomized controlled trials have found no difference in
long term outcome when systemic therapy is given before
or after surgery, but it has increased the rate of BCT
with no significant change to survival.
◦ (Rastogi et al, 2001)

54. SYSTEMIC TREATMENT
◦Rationale for Neoadjuvant Chemotherapy
a. Render an inoperable tumour resectable
b. Downstage an operable tumor for BCT
c. Provide important prognostic information based on
response to therapy.
d. Allows time for appropriate genetic testing
e. Allow time for planning of breast reconstruction
following surgery

55. SYSTEMIC TREATMENT
◦ Candidates for Neo-adjuvant Chemotherapy
◦ Locally advanced or inoperable tumours
◦ Bulky or matted cN2
◦ cN3 regional lymph nodes
◦ cT4 tumors
◦ Patients with operable tumors who desire BCT
◦ Patients in whom definitive surgery may be delayed
Contraindication
◦ Patients with extensive in-situ carcinoma when extent of
invasive disease cannot be defined.
◦ Tumors not palpable or clinically assessable

56. SYSTEMIC TREATMENT
CYTOTOXIC CHEMOTHERAPY
◦Anthracyclines – Adriamycin, Epirubicin
◦Taxanes -- Paclitaxel, Docetaxel
◦Antimetabolite – Capecitabine (Xeloda)
◦Platinum bases -- Carboplatin and
cisplatin
◦Alkylating agent – Cyclophosphamide
◦Vinca alkaloids -- Vinblastine

57. SYSTEMIC TREATMENT
MOLECULAR TARGETED THERAPY
◦ Adjuvant Chemotherapy for HER-2 Positive Breast
Cancer
◦ Can be given Neo-adjuvantly with cytotoxic
chemotherapy
◦Medications
◦ Trastuzumab (Herceptin)
◦ Pertuzumab
◦ Lapatinib,
◦ Ado-trastuzumab (formerly called T-DMl)
◦Duration - 12 months

58. SYSTEMIC TREATMENT
MOLECULAR TARGETED THERAPY
Adjuvant Chemotherapy for HER-2 Positive
Breast Cancer
◦In the ALTTO and APHINITY trial combining
◦ Dual combination of (Trastuzumab and Pertuzumab)
◦ Significant improvement in disease free survival
◦ Improvement comes at expense of toxicity, longer
treatment and cost

59. SYSTEMIC TREATMENT
HER-2 POSITIVE TUMORS
Preferred Regimen
1. Paclitaxel + Trastuzumab
2. Docetaxel + Carboplatin + Trastuzumab
3. Docetaxel + Carboplatin + Trastuzumab +
Pertuzumab
Other Recommended Regimen
1. AC + Docetaxel + Trastuzumab
2. AC + Docetaxel + Trastuzumab + Pertuzumab

60. SYSTEMIC TREATMENT
HER-2 NEGATIVE TUMORS
◦Preferred Regimen
1. AC followed by Paclitaxel
2. Docetaxel and Cyclophosphamide
3. Pre-op Pembrolizumab + [Cisplatin + Paclitaxel] +
Adjuvant Pembrolizumab
4. Capecitabine (Xeloda)
5. Olaparib
There is still no “best” agent or
combination for treatment

61. SYSTEMIC TREATMENT
HORMONAL THERAPY
◦Indications
◦ Prevention of breast cancer
◦ Patients who have ER and/or PR positive tumours
◦ Neoadjuvant use: To shrink large ER+ tumours and
make them operable.
◦ Adjuvant treatment: this is the usual mode of
treatment.
◦ For palliation in patients with metastatic disease.

62. SYSTEMIC TREATMENT
HORMONAL THERAPY
◦ Modalities of Hormonal Therapy
1.Ablative endocrine therapy - LHRH
Agonist(Goserelin), oophorectomy, adrenalectomy
2.Selective Oestrogen Receptor Modulator – e.g.,
Tamoxifen, Raloxifene,
3.Selective Aromatase Inhibitors (AI) – e.g.,
Anastrozole (Arimidex), Exemestane
4.Other anti-oestrogens – e.g., Fulvestrant (Faslodex)

63. SYSTEMIC TREATMENT
HORMONAL THERAPY
◦ Premenopausal women
◦ Tamoxifen for 5 years with or without ovarian
ablation
◦ Ovarian suppression with A1 if Tamoxifen is
contraindicated
◦ Post-menopausal women
◦ AI for 5 years
◦ 2 to 3 years of Tamoxifen followed by AI to complete 5
years
◦ 2 to 3 years of AI followed by Tamoxifen to complete 5
years

64. Update on Adjuvant Hormonal
Therapy
From the Oxford University study, ATLAS and
aTTOM trials,
◦ There is an increased risk of recurrence for 5 through 20
years after initial hormonal therapy
◦ There is a greater reduction in recurrence and death when
the Tamoxifen therapy is extended by 10 years.
Recommendation by NCCN
Unless contraindicated, it is now recommended to
extend hormonal therapy to 10 years

65. HORMONAL THERAPY AS A PREVENTIVE
THERAPY
American Society of Clinical Oncology (ASCO) and the
U.S. Preventive Services Task Force have recommended
endocrine therapy for breast cancer prevention.
1.Women with BRCA1 or BRCA2 mutation.
2.Age over 60 years.
3.Age over 35 years with a history of (LCIS), (DCIS),
or atypical proliferative lesions of the breast

66. Bone-Modifying Agents
◦ Postmenopausal patients with HR-positive, HER2-
negative tumors who qualify for systemic treatment
regardless of bone mineral density.
◦ Large meta-analysis has revealed that specific
bisphosphonates (IV zoledronic acid and oral
clodronate) decrease recurrent breast cancer risk
(primarily risk of bone metastasis) and improve
Overall Survival.
◦ (Fletcher et al 2017; Hadji et al 2016)

67. Current NCCN
recommendations
1. Carcinoma in-situ
◦ Wide local excision without ALND followed by Radiotherapy
◦ OR
◦ Total Mastectomy with or without SLN biopsy + Reconstruction
2. For Early Breast ca to Operable Locally Advanced Breast
Cancer
◦ Neoadjuvant chemotherapy with an anthracycline-containing or
taxane-containing regimen or both
◦ Mastectomy or Lumpectomy with axillary lymph node dissection if
necessary
◦ Adjuvant radiation therapy
◦ Targeted and hormonal therapy if tumor meets biological criteria

68. Current NCCN
recommendations
3.For inoperable stage IIIA and for stage IIIB
breast cancer
◦ Neoadjuvant chemotherapy reduce the local-regional
cancer burden.
◦ Neoadjuvant treatment may permit modified radical or
radical mastectomy,
◦ Adjuvant radiation therapy
4. For metastatic disease (Stage IV)
◦ Systemic therapy is the mainstay of treatment based on
molecular subtype
◦ Locoregional therapy with surgery and/or radiation is

69. ONCOPLASTIC SURGERY
Types of Reconstruction
• Use of implant – silicon or saline implants
• Autogenous tissues -- use of flaps and tissue expanders
• Composite – Both implants and autogenous reconstruction
Timing of Reconstruction
• Immediate Reconstruction
• Delayed Reconstruction

70. RISK FACTOR MANAGEMENT
◦Screening for Breast Cancer
1. Breast Self-Examination
2. Clinical Breast Examination (CBE)
3. Mammographic Screening
4. Genetic Screening
◦ Prophylactic Treatment
1. Tamoxifen
2. Prophylactic bilateral mastectomy

72. REFERENCES
Breast Tumours - WHO Classification of Tumours, 5th Edition, Volume 2 (2019)
NCCN Guidelines Version 8.2021.
Schwartz's Principles of Surgery, 10th Ed
Vanderpuye et al. Infectious Agents and Cancer (2017) 12:13 DOI 10.1186/s13027-017-0124-y