KEY NOTES CHAPTER 4: THE BREAST AND CHEST WALL - Breast Cancer.

Question 0

What are the risk factors for breast cancer?

Answer 0

Reproductive factors
• Early menarche; late menopause.
• Age >30 at first childbirth.
• Low / nulliparity.
• Exogenous hormones (OCP, HRT).

Breast factors
• High breast density
• Previous breast cancer.
• Atypical ductal and lobular hyperplasia (ADH).
• Lobular in situ neoplasia (LISN)
• Previous breast irradiation (e.g. lymphoma).

Genetic factors
Family history
• 1 affected first degree relative: risk doubled.
• 85% have no family history.

Gene mutations
• Mutations in BRCA1 and BRCA2 (4+ family members).
• 1 in 450 women
• ~ 2% of all breast cancers.
∘ Mutations show autosomal dominant inheritance.
• BRCA1
∘ 65% risk of breast cancer and 46% risk of ovarian cancer by 70.
• BRCA2
∘ 57% risk of breast cancer and 23% risk of ovarian cancer by 70.
• TP53 gene (Li-Fraumeni syndrome)
• PTEN gene (Cowden’s syndrome).

Other factors
• Age (80% cases are >50)
• Increased body weight.
• Lack of physical activity.
• Excess alcohol.
• Caucasian.

Question 1

What is the epidemiology of breast cancer?

Answer 1

UK

• most common cancer, 15% of all cancer deaths.
• 157:100,000 women
• 1:8 lifetime risk
• mortality is decreasing (? earlier diagnosis, more effective Rx, less HRT use).

Question 2

How are breast cancers classified?

Answer 2

1. Distribution within breast
(multifocal= 2+ foci within one breast quadrant, multicentric = 2+ foci within different breast quadrants.)
2. Histological type
3. Tumour grade
4. TNM stage
5. Receptor status.

Question 3

How are tumours classified by histological type?

Answer 3

Histological type
1 Non-invasive tumours
2 Invasive tumours.

Non-invasive tumours
(a) Ductal carcinoma in situ (DCIS)
• dysplasia confined to epithelial cells of mammary ducts. Bilateral in 10%; multicentric 20%.
• ~ 60% become invasive.
• Small -> WLE, large -> mastectomy.

(b) Lobular in situ neoplasia (LISN) (prev LCIS).
• Usually occult
• Marker, rather than precursor of breast cancer.
• Bilateral in 40%; multifocal in 60%.
• Risk of breast cancer ~ 1% per year.
• Bilateral risk-reducing mastectomy considered.

Invasive tumours

(a) Ductal carcinoma (80%)
(b) Lobular carcinoma (10%) - bilateral likely.
(c) Medullary
(d) Tubular
(e) Papillary
(f) Mucinous
(g) Adenoid cystic.

Question 4

Describe the grading and TNM classification of breast cancer.

Answer 4

Grade
• Scored on tubule formation, nuclear pleomorphism and mitotic count:
∘ Grade 1 (well differentiated, low grade)
∘ Grade 2 (moderately differentiated, intermediate grade)
∘ Grade 3 (poorly differentiated, high grade).

Primary tumour (T)
• Tis: in situ
• T1: ≤20mm
• T2: tumour >20mm but ≤50mm
• T3: tumour >50mm
• T4: any size with direct extension to chest wall±skin

Regional lymph nodes (N)
• N0: none
• N1: mobile ipsilateral level I, II axillary lymph node(s)
• N2a: ipsilateral level I, II matted axillary lymph nodes
• N2b: clinically detected ipsilateral internal mammary without axillary
• N3a: ipsilateral infraclavicular
• N3b: ipsilateral internal mammary and axillary
• N3c: ipsilateral supraclavicular

• M0: no distant metastases
• cM0(i+): no clinical or radiographic evidence but deposits of molecularly
or microscopically detected tumour cells in blood, bone marrow or other
nonregional nodal tissue <0.2mm, asymptomatic.
• M1: distant detectable metastases > 0.2mm.

Question 5

How is breast cancer staged?

Answer 5

.

Question 6

What is the prognosis of breast cancer according to stage?

What prognostic tools are available?

Answer 6

AJCCS 5 yr survival rates
∘ Stage I: 92%
∘ Stage II: 73%
∘ Stage III: 50%
∘ Stage IV: 13%.

Prognostic tools

1. Nottingham Prognostic Index (NPI)
2. Adjuvant! online prognostication and treatment benefit tool
3. PREDICT online breast cancer survival tool.

Question 7

What receptors are tested for and how?

Answer 7

∘ Oestrogen receptor (ER) (70%+)
∘ Progesterone receptor (PR)
∘ Human epidermal growth factor receptor 2 (HER2/neu). 15% cancers are +ve and may respond to trastuzumab (Herceptin®).

By immunohistochemistry (IHC) or fluorescence in situ hybridisation (FISH).

Question 8

How is breast cancer diagnosed?

Answer 8

Triple assessment:

1. Clinical examination
2. Imaging - mammography and/or ultrasound with MRI as required
3. Biopsy - FNAC or needle core biopsy

Question 9

What are the different types of imaging for breast cancer diagnosis?

Answer 9

1. Mammography
   - UK NHS BSP: 3-yearly mammographic screening to women 47 - 73.
   - Suspicious signs:
   ∘ Microcalcification
   ∘ Density changes
   ∘ Asymmetry
   ∘ Architectural distortion.
   - Eklund views: for patients with implants.
2. Ultrasound
   - Useful, particularly in younger patients & more fibrous breasts, to differentiate between solid and cystic lesions.
   • Allows assessment, measurement and aspiration/biopsy.

MRI if
∘ discrepancy between clinical and radiological estimated extent of disease.
∘ dense breast pattern on mammography.
∘ Core biopsy suggests invasive lobular cancer.

MARIA
• Multistatic Array Processing for Radiowave Image Acquisition (MARIA): more comfortable than mammogram, suitable for
different breast densities.

Question 10

What are the modes of treatment for breast cancer?

Answer 10

Usually multimodal
∘ Surgery
∘ Radiotherapy
∘ Chemotherapy
∘ Hormonal therapy
∘ Biological therapy.

Question 11

What are the different types of surgical exicisions?

Answer 11

Primary tumours
• Breast conserving surgery
∘ Wide local excision (WLE)
∘ Quadrantectomy

• Mastectomy
(a) Radical (breast, pec major + minor, ALND)
(b) Extended radical (+intrapleural IMLN)
(c) Modified radical (pec preserved)
(d) Simple - entire breast without axillary nodes e.g.
∘ T3 or T4 tumours
∘ T2 tumours in small breasts
∘ Multicentric tumours
∘ Widespread DCIS.
(e) Skin sparing
∘ 90-95% breast tissue excised, periareolar / Wise pattern excision or depithelialisation & implant cover (for large breasts)
(f) Nipple sparing
∘ tumours <3 cm, located far from the nipple with favourable pathological features and no axillary disease.

Question 12

What are the most common types of immediate breast reon

Answer 12

∘ Subpectoral implant / expander + ADM
∘ Implant / expander + LD flap.
∘ Extended LD flap +/- subsequent lipofilling.
∘ De-epithelialised TRAM or DIEP flap.

Question 13

What are the indications for axillary clearance?

Answer 13

Indications for axillary clearance:

1. Positive pre-operative FNAC or ultrasound-guided biopsy.
2. Positive SLNB, either macro or micrometastases.

• Treatment: axillary clearance or radiotherapy.

• The significance of isolated tumour cells in lymph nodes is uncertain.
∘ Currently, such patients are regarded as lymph node negative.
∘ Axillary clearance is not recommended.

Question 14

How is the axilla staged?

Answer 14

Pre-op axillary US +/- FNAC / core biopsy. If -ve:

1 SLNB: combined radioisotope and blue dye
technique.

2 Axillary node sampling.
- Removes part of level 1, at least 4 lymph nodes.

Question 15

When is radiotherapy indicated?

Answer 15

Breast
• Primary invasive breast cancer treated with breast conserving surgery.
• DCIS treated with breast conserving surgery.
• Chest wall radiotherapy for high risk disease, such as:
∘ Large tumour
∘ High grade tumour
∘ ≥4 positive axillary lymph nodes
∘ Involved resection margins.

Axilla
∘ +ve disease on ALNS (but NOT together with clearance)

Question 16

What are the LN different levels of axilla?

Answer 16

• Levels of the axilla are defined anatomically, based on pectoralis minor:
∘ Level I: inferolateral to pectoralis minor.
∘ Level II: behind pectoralis minor.
∘ Level III: superomedial to pectoralis minor.

• Level I-III clearance is effective in controlling regional disease, with recurrence rates of
3-5% at 5 years.
• The Edinburgh study showed a similar rate of control is achievable with adjuvant radiotherapy
following axillary sampling (but no additional staging information).

Question 17

What types of hormonal therapy are there?

Answer 17

∘ Tamoxifen
∘ Aromatase inhibitors (anastrozole, exemestane, letrozole)
∘ Progestogens
∘ LHRH analogues
∘ Oophorectomy by radiotherapy, laparoscopy or open surgery.

Tamoxifen
• ER antagonist in breast tissue via its active metabolite, hydroxytamoxifen.
• Partial agonist in endometrial tissue.
∘ Linked to endometrial cancer in some women.

Aromatase inhibitors
• Prevent conversion of androgens to oestrogen in peripheral tissues
∘ Do not stop oestrogen production in ovaries.
• Considered in postmenopausal women with ER positive tumours.
• Can lead to osteopenia

Question 18

When is chemotherapy indicated?

Answer 18

• Lymph node +ve
• Large primary tumour
• High grade (grade 3) tumour
• ER negative, HER2 positive.
• Chemotherapy can be used as:
∘ Neoadjuvant - reduce tumour preop.
∘ Adjuvant - to prolong disease-free survival in early breast cancer,
especially pre-menopausal women with ER negative tumours.
∘ Treatment for recurrence.

Question 19

What is Herceptin?

Answer 19

• Trastuzumab is a monoclonal antibody to HER2 receptor.
• Reduces relapse of HER2 positive breast cancer by 50% and mortality by 30%.
• Can cause cardiac toxicity.

Question 20

How is breast reconstruction classified?

Answer 20

Timing
• Immediate
• Delayed
• ‘Delayed immediate’
∘ preservation of skin envelope with expander until histology.
∘ If radiotherapy not required, expander is removed and reconstruction performed.
∘ If radiotherapy required, reconstruction is delayed.

Amount of tissue resected
• Partial breast reconstruction - after BCS.
1 Volume replacement - transferring tissue into breast.
2 Volume displacement - rearranging breast tissue to fill defect.
• Complete breast reconstruction - after mastectomy.

Reconstructive options
• Oncoplastic techniques.
• Breast implant or expander + flap/ADM.
• Flap reconstruction alone.
• Lipomodelling.

Question 21

How did Clough classify different oncoplastic techniques?

Answer 21

Level I: ≤20% breast volume loss.

• Reconstruction based on dual plane undermining of the gland followed by glandular reapproximation.
• No skin excision required.
• The NAC repositioned by de-epithelialising crescent adjacent to areola.

Level II: 20-50% breast volume loss.
- ‘therapeutic mammaplasties’ based on breast reduction techniques to reshape breast and excise skin.

Question 22

Tell me about implant or expander based breast reconstruction.

Answer 22

suitable for small breast reconstructions with healthy, non-irradiated skin flaps.

Question 23

What happens when tissue expanders are placed subpectorally after mastectomy?

Answer 23

∘ Difficulty controlling lower pole of pocket during expansion.
∘ Unprotected coverage by thin inferior mastectomy flap.
∘ Effacement of IMF.
∘ Limited control of superior migration of pectoralis major.

• Inferolateral support and soft tissue coverage of implants is improved by:
∘ Adjacent local tissues - muscle or fascia.
∘ De-epithelialised skin from a Wise pattern mastectomy.
∘ ADM.

Question 24

How can the limitations of implant / expander only reconstructions be resolved?

Answer 24

Implants can be placed under a transposed LD myocutaneous flap or ADM.

Question 25

What is your patient selection for ADM + implant reconstruction?

Answer 25

Suited for small - medium breast recons.
Higher complication rate in large breasts, smokers, and obese patients.

ADM uses:

• extend subpectoral plane
• support implant in an antomical position (hammock)
• defines the inferior and lateral folds of the breast

Question 26

How do you perform an implant + ADM reconstruction after SSM?

Answer 26

1 stage (immediate)

1. Develop a standard subpectoral pocket.
2. ADM is sutured to IMF with 2/0 PDS, corners 1st then in between into a dome shape (like a parachute).
3. An implant is placed in this muscle-ADM pocket.
4. ADM is then sutured to inferior border of pectoralis major with vicryl 3/0.
5. Drain is placed between ADM and skin, and skin is closed with no tension.

If significant skin was excised or vascularity of mastectomy flaps questionable, place tissue expander in pocket and do 2 stage op.

Question 27

What are the advantages and disadvantages of using ADM?

Answer 27

Advantages:
∘ Reduced soft tissue dissection for inferior pole coverage.
∘ Improved lower pole expansion, better control of breast shape.
∘ Reduced rates of capsular contracture.
- A study of 260 patients reported rates of 0.4% after 29 months mean follow-up.

• Disadvantages:
∘ Seroma (5%)
∘ Infection (5%)
∘ Reconstructive failure (4%)
∘ Possible need for prolonged drainage.

Question 28

What are the common flap donor sites for breast reconstruction?

Answer 28

Back

• LD (muscle, myocutaneous, extended)
• TDAP

Chest wall
- ICAP: Can be based on:
∘ Vertebral segment - dorsal intercostal artery perforator (DICAP).
∘ Costal segment - lateral intercostal artery perforator (LICAP).
∘ Muscular or rectal segment - anterior intercostal artery perforator (AICAP).

• Thoracoabdominal advancement flap (inferior pole)

Abdomen
- DIEP
- SIEA
- TRAM (free, pedicled, muscle-sparing, delay, super or turbocharged to thoracodorsal axis)
(- omentum)

Flank/buttock

• IGAP (better scar than SGAP)
• SGAP
• Rubens (deep circumflex iliac)

Thigh
- TUG: transverse upper gracilis

Question 29

.

Answer 29

• Based on the deep inferior epigastric artery (DIEA) and vein.
• The DIEA usually divides into two branches, giving perforators in medial and lateral rows:
∘ Lateral branch dominant ~ 50%.
∘ Medial branch dominant ~ 7%.
∘ Equal dominance ~ 15%.
∘ Single axis + multiple side-branches ~ 28%.

• >90% of major perforators are within 6 cm area inferolateral to umbilicus.

• The skin paddle is divided into four zones:
∘ Zone 1 - over ipsilateral rectus abdominis; receives perforators from DIEA.
∘ Zone 4 - the extreme opposite side of abdomen supplied by contralateral superficial circumflex iliac artery (SCIA) - discarded.

∘ Hartrampf (1982): zone 2 = contralateral midline, zone 3 = lateral to zone 1.
∘ Holm (2006): zone 2 = lateral to zone 1, zone 3 = contralateral midline.

Blood supply to area lateral to zone 1 = SCIA. anatomical territory, + blood from DIEA through choke vessels.

Contralateral midline = its own DIEA, + dynamic area of opposite DIEA.

Contraindications:
• After abdominoplasty or abdominal liposuction.

Question 30

What are the techniques for nipple reconstruction?

Answer 30

Prosthetic (adhesive)

Autologous

• Usually as a secondary procedure under LA.
• Allow patients to attempt positioning nipple with ECG dots and bra on.

Nipple sharing
- Composite graft from contralateral nipple (if large).

Local flaps

• CV flap (Bostwick 1998)
• Skate flap + FTSG (Little 1984)
• Star flap (modification of Skate, no FTSG required)
• Quadripod flap (Little 1983)
• Double-opposing tab (DOT) flap

Cartilage grafts

• wrapped under flap reconstruction to maintain projection.
• Donors: costal cartilage banked from DIEP op, ear.

Risks: resorption, infection, extrusion, donor site morbidity.

Question 31

How can the areolar be reconstructed after nipple is made?

Answer 31

Tattoo

FTSG (contralateral NAC, labia majora has been described).