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
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
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
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.
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
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
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)
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
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
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.
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
71.
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
Notas del editor
According to the WHO Globocan, Breast cancer is the malignancies with the most prevalence and incidence
Lifestyle that reduce the risk of breast cancer
Under- reporting
Ghanaian women frequently present with advanced stage breast cancer and experience poor outcomes
Averagely 125 cases are diagnosed by the pathology team every per year (
Modified sweat gland Lat border to sternum to MAL
2nd -- 6th rib
Fascia of pectoralis major and serratus anterior
Age -- Rare before age 20 Incidence rises from age 30 to 80
West African women is between 35 and 45 years, 10 to15 years earlier than in women from high-
Geographic patterns – reproductive, lifestyle , diet, breast feeding habits
Predominantly affect female (incidence males – 1% of that in women)
BRCA 1 (Ch 17q) associated with ovarian, colorectal and prostate ca
Other genes - ATM. PTEN, CHEK2, LKB1 and p53.
Tend to develop ca at younger age, affects both breast
Breast feeding for a long duration and increased partly reduce the risk
Breast feeding for a long duration and increased partly reduce the risk
Although, these lesions are low grade, there is a 25% to 35% risk for development of invasive carcinoma
in the same or the opposite breast (greater for the ipsilateral breast).
Marked increase in the dense fibrous tissue stroma produces the characteristic hard “scirrhous” appearance of the typical infiltrating ductal carcinoma
(axillary tail of breast or the lymph nodeThe upper outer quadrant is the commonest site (50%)
Palpable masses are almost always invasive and typically (2-3cm) in size.
At least half of these cancers will already have spread to the lymph nodes
May be painful in flammatory carcinoma
The upper outer quadrant is the commonest site (50%)
Palpable masses are almost always invasive and typically (2-3cm) in size.
At least half of these cancers will already have spread to the lymph nodes
May be painful in flammatory carcinoma
Mammogram - useful in breast that contains little dense glandular tissue and composed predominantly of fat
About I0-15 % of breast cancers are not seen on mammography.
It can detect unexpected breast cancer is asymptomatic patients hence it supplement clinical history and examination
A solid mass with or without stellate,
Asymmetric thickening of breast tissues, and
clustered microcalcifications.
A small, spiculated mass is seen in the right breast with skin tethering
Mammogram - useful in breast that contains little dense glandular tissue and composed predominantly of fat
About I0-15 % of breast cancers are not seen on mammography.
However, in the circumstance of negative findings on both mammography and physical examination, the probability of a breast cancer being diagnosed by MRI is extremely low.
Imaging guidance reduces risk of sampling errors.
A radiopaque marker should be placed at the site of the biopsy to mark the area for future intervention.
Breast feeding for a long duration and increased partly reduce the risk
Incorporating the prognostic stage into the breast cancer staging system has allowed physicians to individualize the patient prognosis, leading to a more optimal estimation of prognosis.
The multigene panel is used to evaluate 16 genes and five reference genes, in order to predict the likelihood of recurrence in patients undergoing endocrine therapy alone,
In general,
Triple-negative tumors are “upstaged” in their prognostic stage, and
HER2 expression is a “downstaging” factor (due to the success of anti-HER2 therapies).
The aims of local or loco-regional treatment are:
to eradicate local or regional breast cancer.
to prevent local recurrence.
to minimise distant spread (metastatic cells).
In both types of surgery the ax ilia is investigatedand/onreated by needle biopsy, sentinel node biopsy or axillary node clearance
In both types of surgery the ax ilia is investigatedand/onreated by needle biopsy, sentinel node biopsy or axillary node clearance
Total mastectomy is advised if margins are still not clear after 2nd surgery
Clears the axilla of any tumor deposits and allows for a more accurate staging
A review surgery can be done if margins are still not clear after index surgery
Axilla clearance - any clinically or radiologically evident lymph nodes
Sentinel lymph node biopsy – for undetectable lymph nodes.
SLN is performed before removal of the primary breast tumor.
Specimen x-ray should routinely be performed to confirm the lesion has been excised and that there appears to be an appropriate margin.
absence of any ink on the excised tumor
BCT allows for preservation of breast shape and skin as well as preservation of sensation, and provides an overall psychologic advantage associated with breast preservation.
The use of systemic
chemotherapy and hormonal therapy as well as adjuvant radiation therapy for breast cancer have nearly eliminated the need
for the radical mastectomy
In a skin-sparing mastectomy, all of the breast skin, except the nipple and the areola is preserved
A pathologic confirmation of malignancy for clinically positive nodes is necessary using USG guided FNAC or Core Biopsy of Suspicious node before ALDN is indicated
For Stage I and II Breast Cancer with 1 or 2 positive SLN who have had WLE and no pre-operative treatment but are to have whole breast radiotherapy, there is no need for further axillary clearance
INumerous strategies to reduce the toxicity and duration of radiotherapy are being explored
Examples
hypofractionated radiotherapy,
partial breast irradiation,
intraoperative radiotherapy
Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): Adjuvant radiotherapy for
. Principal goal - eliminate microscopic metastatic disease
Extent of the tumor is poorly delineated
TCH (docetaxel [Taxotere] and carboplatin combined with trastuzumab [Herceptin])
TCH (docetaxel [Taxotere] and carboplatin combined with trastuzumab [Herceptin])
weighed against
the additional toxicity (increased diarrhea,
rash, etc), longer treatment sessions, and
increased costs when making adjuvant treatment
decisions.
Pembrolizumab works by inhibiting lymphocytes PD-1 receptors, blocking the ligands that would deactivate it and prevent an immune response.
Endocrine therapy is recommended after completion of chemotherapy for patients who are also HR-positive
(Goserelin- Zoladex)
If woman is postmenopausal at end of 5 years of Tamoxifen – AI is started for 5 years
Traditionally , adjuvant endocrine therapy is recommended for at least 5 years.
It is indicated in women at high risk of breast cancer, including the following:
Adjuvant bisphosphonate therapy should be
Sometimes the other breast will have to reconstructed to ensure uniformity
Reconstruction is best deferred if patient is to have adjuvant radiotherapy
Current guidelines of the National Comprehensive Cancer Network suggest that normal-risk women ≥20 years of age should have a breast examination at least every 3 years. Starting at age 40 years, breast examinations should be performed yearly and a yearly mammogram should be taken. The benefits from screening mammography in women ≥50 years of age has been noted above to be between 20% and 25% reduction in breast cancer mortality