Cancer of the Breast.pdf a surgical aspect

Cancer of the
Breast
Dr Wanjara
Consultant General Surgeon
8th March, 2024

Outline
• Introduction
• Risk Factors
• Pathology
• Clinical Presentation
• Staging
• Treatment
• Surgical Principles
• Special Circumstances—Recurrence, Pregnancy, Male Breast, Inflammatory
breast cancer, Sarcoma
• Screening

Principle Number 2
Name it, Stage it, Treat it!
• MDT
[Surgeon, radiologist, pathologist, radiation oncologist, medical oncologist, plastic surgeon and allied health
professionals, such as a breast care nurse, psychological counsellor and preferably a genetic counsellor ]

Introduction
• Most common cancer in women
• In resource-poor countries;
✓ 1 in 28 women will develop
breast cancer in her lifetime
✓For every 2 women diagnosed
with breast cancer, 1 dies of
cancer.

Pathology
• Can be ductal (arise from duct) or Lobular (arise from lobule)
• Can be DCIS or Invasive carcinoma

Pathology; Grading
• Can be well, moderately or poorly
differentiated
• The Modified Bloom–
Richardson scoring system for
tumour grade
A total score of 3–5 defines grade I; 6 or 7 grade II; and 8 or 9 grade III.

Pathology; Histological variants
• NOS/NST [no special type]-----commonest
• Mucinous---produce mucin
• Medullary—large solid sheets of cells with
lymphocytic reaction
• Papillary--- has papillomas with a fibrovascular
core and surface covered by epithelial and
myoepithelial cells|Rarely spreads to
lymphatics|Has better prognosis
• Tubular carcinoma

Pathology; Molecular subtypes
• Rationale;
-Prognostication
-Individualizing treatment
• Tumour cells may overexpress
(i) Oestrogen receptors (ER positive)
(ii) Progesterone receptors (PR positive)
(iii) Human epidermal growth factor receptor 2/neu (HER2/neu positive)
(iv) Androgen receptors (AR positive).
• The degree of mitosis can be detected by the Ki-67 mitotic index.
• Can be determined by;
✓ Gene Array analysis [aka GEP; Gene expression profilling]
✓ Prediction Analysis of Microarray [PAM-50]
✓ Immunohistochemistry [IHC]

Pathology; Triple Assessment; Tissue diagnosis

Pathology; Spread
• Local
• Lymphatic
• Hematogenous
[Probable order; lumbar vertebrae, neck of femur, thoracic
vertebrae, rib and skull ]
• Study of Peripheral blood samples for circulating
cell-free tumour deoxyribonucleic acid (cf-DNA)
and circulating tumour cells may offer
(i) Potential prognostic markers to predict disease
recurrence
(ii) More insights in realizing that breast is a systemic
disease

Clinical Presentation
• Lump
• Nipple discharge
• Nipple retraction
• Peau de orange
• Carcnoma en cuirrase
• Abnormal imaging results from
screening
• Remember;
• Lymphadenopathy
• Symptoms suggesting Mets;
[Bony pain, cough, breathlessness, haemoptysis,
headache, visual disturbances, neurological
deficit, epileptic fits, abdominal distension,
jaundice, anorexia, weakness, weight loss,
hypercalcaemia, etc]

Clinical Presentation
• Carcinoma en cuirasse;
carcinomatous lymphatics result in extensive thickening, edema and fibrosis of dermis, and subcutis of
chest wall.

Prognostic factors
• Invasive or In situ
• Tumor size [T]
• +/- Lymph node Mets [N]
• +/- Distant Mets [M]
• ? Locally advanced
• ?Inflammatory carcinoma
Others;
• Histology subtype
• Tumor grade
• Receptor status
• Lymphovascular invasion
• Proliferative rates

Staging
• American Joint Committee on Cancer (AJCC) TNM
staging system is currently used
Note;
Inflammatory breast cancer regardless of size; T4d
• Done by
-CT scan of Chest, Abdomen, Pelvis
-FDG-PET
-Bone scans

Treatment of Breast Cancer
• Early [T1,T2,No,Mo]
-Upfront surgery
-+/- Adjuvant therapy [Systemic therapy or Radiotherapy]
• Locally advanced [≥T3, ≥N1,Mo]
-Neoadjuvant therapy [Systemic therapy or Radiotherapy]
-Surgery
-Adjuvant therapy [Systemic therapy or Radiotherapy]
• Metastatic [Any T, Any N, M1]
-Palliative therapy [Systemic therapy or Radiotherapy]
-+/-Palliative surgery

Neoadjuvant Systemic Therapy
Why?
• Downsize
• Assess response
What?
• Systemic therapy [Include; Targeted
therapy, hormonal therapy,
Chemotherapy] or Radiotherapy
• Neoadjuvant targeted therapy (Trastuzumab, Pertuzumab) for
HER2/neu-positive tumours >5 mm in diameter.
• Neoadjuvant hormonal therapy is offered to hormone receptor +ve
elderly or frail women who are deemed unfit to receive systemic
chemotherapy.
Who?
a) Locally advanced breast cancer [≥T3, ≥N1,Mo]
: to downsize the tumour
b) Cases of early breast cancer:
*To downsize the tumour to facilitate breast
conservation surgery (BCS);
*HER2/neu-positive tumours;
*Triple-negative breast cancer (TNBC);
*Premenopausal women (age <50 years);
*Patients with axillary node metastasis.

Neoadjuvant Systemic Therapy
• How to assess for response ; Radiological

What if the response is CR and surgery is needed?
• Magseed
• Wire guided localization
• Radioactive seed
• Radiofrequency guide
• Others

Surgery
No difference in outcomes between Mastectomy and WLE/BCS +
Radiotherapy

Surgical Options
• Goal; to remove all disease in the breast and axilla with negative margins.
• How?
a) Lumpectomy/Quadrantectomy/WLE
b) Mastectomy; [removal of the entire breast tissue, including the skin over the tumour, the nipple–areola complex and the
axillary tail]
• Mastectomy indicated for;
-Large tumours (in relation to the size of the breast)
-Multicentric disease,
-Difuse micro-calcifcation on a mammogram indicative of DCIS,
-BRCA-positive cancers,
-Local recurrence following BCS
-The patient’s preference.
• Types; Radical|Modified radical|Skin sparing|Nipple-sparing mastectomy

Breast Conserving Therapy (BCT)
• BCT= BCS + Radiotherapy
• BCS =
WLE/Lumpectomy/Nippple
Sparing or Skin Sparing +/-
Reconstruction

Modified Radical Mastectomy
• Mastectomy + Axillary clearance
[Dissection of Level I, II +/- III
axillary nodes]

Axillary Surgery
• Sentinel Lymph Node Biopsy
[SLNB]
Contraindicated in patients with;
-Inflammatory breast cancer
-patients with T4 disease
-patients a history of previous breast or chest wall
surgery, breast scarring (burns) or radiotherapy.
• Axillary Node Clearance
For clinically Node positive tumors
For Positive SLNB

Complications
• Hemorrhage
• Seromas
• Hematomas
• Infection
• Nerve Injury
• Wound breakdown/Skin Necrosis
• Implant failure
• Lymphedema
• Stewart-Treves Syndrome

Stewart-Treves Syndrome
• Lymphangiosarcoma

Adjuvant therapy
Systemic therapy
• To control micrometastases, delay relapse and
prolong survival
• Includes;
✓Chemotherapy
✓Hormonal therapy
✓Targeted therapy
Radiotherapy
• Decrease the risk of locoregional and systemic
recurrence and improve survival.
• For patients with;
✓ Locally advanced breast cancers T3, T4, N1, N2,
N3 disease
✓ Following BCS;
✓ After mastectomy if:
*tumour size ≥5 cm; skin or chest wall involvement;
Lymphovascular invasion (LVI), grade 3;
*axillary lymph node positive for metastasis.

Adjuvant therapy; Systemic Therapy
Systemic Chemotherapy
• Indicated for;
✓ all invasive carcinomas >1 cm in diameter
✓ tumours >0.5 cm with poor prognostic factors
(presence of LVI, high grade
✓ HER2/neu positive
✓ TNBC)
✓ Node-positive tumours.
• Regimens;
✓ cyclophosphamide (C), methotrexate (M) and 5-fuorouracil (F) (CMF)
✓ Anthracycline-based regimens: CAF (A, Adriamycin [doxorubicin]), CEF (E,
epirubicin)
✓ Taxane (docetaxel, paclitaxel)-based regimens
• Hormonal therapy
• Agents; tamoxifen and Aromatase Inhibitors
(anastrozole, letrozole, exemestane )
✓ Pre-menopausal low risk; Tamoxifen for 5 years
✓ Pre-menopausal low risk; Tamoxifen for 10 years
✓ Post-menopausal; Aromatase Inhibitors
• Targeted therapy
✓ Targets HER-2 Neu receptor
✓ Agents;
-Transtuzumab [Herceptin]
-Pertuzumab
-T-DM1
-Emtansine

Special Circumstances
• Metastatic carcinoma
• Local Recurrence
• Hereditary and Familial Breast Cancer
• Pregnancy
• Male Breast
• Inflammatory breast cancer
• Sarcoma

Metastatic carcinoma
• Goals of care;
✓ Palliating symptoms
✓ Improving quality of life
✓ Preventing potential disabling complications and attempting to
prolong life.
• How?
• Endocrine therapy for hormone receptor-positive disease is for
patients with bony metastasis and limited visceral metastasis.
• Systemic chemotherapy is for patients with hormone receptor-
negative cancers, hormone-refractory metastases and patients
with visceral crisis.
• Radiotherapy and Biphosphonates for painful bone mets or
bone mets in weight bearing areas
• Assignment
1) Mechanism of action of Biphosphonates
2) Mirel’s Criteria

Local Recurrence
• Tripple Assessment
• Name it, Stage it, Treat it!
• MDT

Hereditary and Familial Breast Cancer
• Difference?
• Hereditary Breast Cancer;
✓ More aggressive|Present at an earlier age|More
often multicentric and bilateral.
✓ BRCA1 and BRCA2 involved
✓ Risk reducing mastectomy for women with BRCA
mutation? ↓90%
✓ Chemo-prophylaxis with tamoxifen or anastrozole?
↓50%
✓ Premenopausal women may be ofered bilateral
salpingo-oophorectomy after they have completed
their family at around 35–40 years of age.

Breast cancer in Pregnancy
• Pregnancy associated with aggressive tumour biology such as TNBC
• Ultrasonography of the breast, mammogram and chest radiograph with
abdominal shielding of the fetus may be considered.
• CT and PET-CT should be avoided (high radiation dose).
• Surgery can be performed in any trimester
• Mastectomy is preferred during the first and second trimester . Why?
• Chemotherapy should not be administered during the first trimester but
safe later
Anthracyclines and taxanes remain the preferred agents. 5-Fluorouracil
should be avoided. Anti-HER2/neu and endocrine therapy should be given
after delivery, as indicated.

Carcinoma of the Male breast
• Involvement of the nipple–areolar
complex and underlying pectoral
muscles occurs early.
• Name it, Stage it, Treat it!
• MDT

Inflammatory Breast Cancer
• Can masquerade as a mastitis
• Usually has no underlying mass
• Biopsy of skin shows dermal lymphatic
invasion by tumor cells
• Staged as T4d
• ASLB Not indicated
• Neoadjuvant therapy standard
• MRM Standard
• Adjuvant Therapy standard
Tenet; Tripple Assessment|Name it, Stage it, Treat it!|MDT

Breast Sarcoma
• Arise from breast mesenchymal cells
• Most commonly fibrosarcoma and angiosarcoma
• Angiosarcoma is the most aggressive of all breast
tumours
• Risk factors;
✓ genetic conditions (Li–Fraumeni, neurofbromatosis
type 1)
✓ exposure to alkylating agents, vinyl chloride or
arsenic
✓ prior radiotherapy (e.g. for Hodgkin’s lymphoma)
✓ chronic lymphoedema
• Systemic Therapy standard
Tenet; Tripple Assessment|Name it, Stage it, Treat it!|MDT

Breast Cancer Screening
• Age
✓From 40 years
✓Every 1 to 2 years
• Method
✓Breast Cancer Risk Assessment Tool
(BCRAT); Gail Model [www.cancer.gov/bcrisktool/]
✓?CBE and ?SBE
✓Mammogram [Gold Standard]|MRI
• Marker
• ?False positives|?Overdiagnosis

End
Have a wonderful weekend ahead.
Further comments/Questions; drwanjara@gmail.com

Cancer of the Breast.pdf a surgical aspect

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