This woman had mammography after she felt a right breast lump. Mammogram revealed not only the cancer in the right breast (large circle in the left picture), but also an unsuspected cancer in the opposite breast (small circle in the right picture).
Tamoxifen has i) an antioestrogenic effect via blockade of oestrogen receptors and ii) a local antitumour effect, independent of its effect upon oestrogen receptors Locally, tamoxifen decreases the secretion of stimulatory growth factors, such as transforming growth factor alpha (TGF α ). It also increases the secretion of an inhibitory growth factor, such as transforming growth factor (TGF β ) TGF β is also known to inhibit the growth of oestrogen-receptor-negative cells. It is believed that this is how tamoxifen can be effective in oestrogen-receptor-poor tumours Tamoxifen is thought to increase TGF β production in stromal cells in the tumour Tamoxifen may also act by other mechanisms including: i) affecting levels of sex hormones binding globulin ((SHBG) ii) preventing angiogenesis Reference Jordan VC. Tamoxifen. A guide for clinicians and patients. 1996. PPR, Inc. New York
Inhibition of aromatase activity can reduce the growth-stimulatory effects of oestrogens on tumours Whilst aromatase inhibitors are known to be effective in advanced breast cancer, the role of intra-tumoural aromatase activity still remains to be clarified
INTRODUCTION• The common cause of death in middle-aged women in Western countries.• in women amongst all races from the age of 20 years in Malaysia for 2003 to 2005. * Breast cancer is most common in the Chinese, followed by the Indians and then, Malays. * Breast cancer formed 31.1% of newly diagnosed cancer cases in women in 2003-2005.
CLINICAL FEATURES• Breast lump• Dry scaling / red weeping.• Blood stained nipple discharge• Painless• Site : commonly in the upper outer quadrant• Tumour fixation : --Breast distortion-flattening of contour-dimpling or puckering of the overlying skin-Nipple retraction• Nipple eczema in Paget’s disease
• Firm to hard in consistency• Irregular and indistinct edge• Mobile, softer and well circumscribed (esp in mucoid and medullary ca)• In advanced :Skin ulceration Must palpate axillaeInfiltration and supraclavicular areasOedema
DUCTAL CARCINOMA IN SITU• Most DCIS detected by calcifications on mammography/mammographic density - periductal fibrosis surrounding a DCIS/rarely palpable mass/ nipple discharge/incidental finding on a biopsy for another lesion.• Spreads through ducts & lobules extensive lesions entire sector of a breast.• DCIS – involves lobules – acini distorted, unfolded appear as small ducts.
Triple Assessment• All patients presenting with breast symptom should have a full clinical examination• If a localised abnormality is present, >>> mammography and /or ultrasound examination• >>>>core and /or FNAC depending on the clinician’s, radiologist’s and pathologist’s experience. 1955. Belgian Guideline 2007
• In young women (< 40 years old), ultrasound should be the initial imaging modality as part of the triple assessment
MAMMOGRAPHY• a screening tool• Detects:- Lumps- changes in breast tissue- calcifications too small to be found in a physical exam.• Soft tissue radiographs are taken by-placing the breast in direct contact with ultrasensitive film• Very safe investigation -expose to low-voltage.• Sensitivity increases with age (breast become less dense)• Screening procedure – monitoring patients at high risk for breast ca – Women > 40 years• 5% of Br Ca can be missed.• Mammogram: does not exclude Br Ca.
ULTRASOUND• Useful in young women with dense breast.• Distinguish cysts from solid lession• Localise impalpable areas of breast pathology• Not useful as a screening tool
BIOPSY• 3 ways – Fine needle aspiration – Core needle biopsy – Incisional / excisional open biopsy• Microscopic examination
Core Biopsy (CB) incombination with Fine Needle Aspiration Cytology (FNAC)Core biopsy in combination withFNAC may be used where facilityand expertise are available 27
Others• Baseline investigation• detection of metastatic disease: – liver function tests – serum calcium – chest radiograph – isotope bone scan – liver ultrasound scan – CT brain - in cases where suspicion is great clinically
Stage I : T1 N0 M0Stage II A : T1 N1 M0 / T2 N0 M0Stage II B : T2 N1 M0 / T3 N0 M0Stage III A : T1 N2 M0 / T2 N2 M0 / T3 N1 M0 / T3 N2 M0Stage III B : T4 any N M0 / any T N3 M0Stage IV : any T any N M1
MANCHESTER SYSTEM •distant metastases other than the axillary nodes or •satellite nodules on breast or •supraclavicular nodal involvement
EARLY BREAST CAStage I : T1 N0 M0Stage IIA : • T0 N1 M0 Breast conservation is • T1 N1 M0 appropriate. It is an alternative to Mastectomy • T2 N0 M0Stage IIB - T2 N1 M0
Breast conservation• Removal of the tumour only• tumour should be <4cm in size for BCT.• >>>> radiotherapy.• Patient should be willing to take radiotherapy and come for regular follow up.• Absolute contraindications: Pt’s wish to avoid radiotherapy Multifocal invasive breast breast cancer Large tumour in a small breast Widespread of ductal carcinoma in situ. (DCIS)• Then pt needs to do a mastectomy.
RADIOTHERAPY• Improving local control• After BCT for early invasive BC
MASTECTOMY1. Radical Mastectomy (Halsted) • Stage III, IV • Excision of pectoralis major muscle, excision of breast, axillary LN, pect. major & minor • no longer indicated2. Simple mastectomy - – removes breast only, with no dissection of axilla (except for axillary tail - usually attached to a few LN in the anterior group)
MASTECTOMYIndications: Indications: large tumour (( in relation to breast size) large tumour in relation to breast size) central tumours beneath or involved the nipple central tumours beneath or involved the nipple local recurrence local recurrence absolute C/I to radiotherapy absolute C/I to radiotherapy pt’s preference pt’s preference skin/ collagen vascular disease that may be skin/ collagen vascular disease that may be complicated by radiotherapy complicated by radiotherapy inavailability of radiotherapy facilities or non- inavailability of radiotherapy facilities or non- compliance with radiotherapy compliance with radiotherapy
3. Modified Radical Mastectomy: 1. Patey • the whole breast • large portion of skin, the centre of which overlies the tumour, but always include the nipple • all of the fat, fascia, LN of axilla • preservation of axillary vein & nerves to serratus anterior, pectoralis major & latissimus dorsi4 Total mastectomy w/ or w/o radiation: 1. Crile – Total mastectomy 2. Mc Whirter – Total mastectomy and radiation (Axilla, • supraclavicular and internal mammary nodes)
5. Subcutaneous Mastectomy: • Nipple is retained / for T1s5. Quandrantectomy, axillary, radiotherapy (QUART) • Quadrant of the breast that has the CA is resected • (quadrant of breast tissue, skin and superficial pectoralis fascia) • Unacceptable cosmetic result
AXILLARY TREATMENT• At least 4 of LN from axillary fat for analysis.• Can be done w or w/o the removal of pectoralis minor muscle.• Axillary sample- removal of 4/> LN from proximal ant/ pectoral & central gp of draining LN in axilla• Axillary dissection: dissecting the axilla to various anatomical levels- – level I: removal of LN lateral to inferior border of pec. Minor – level II : removal of level I LN & those behind & in front of pec. Minor – level III : removal of all the lymphatic tissue• Axillary clearance ; level III axillary dissection
complications of axillary treatment: intraoperative- damage to nerves postoperative- wound complications, lymphoedema
BREAST RECONSTRUCTION• By plastic surgeons or specialist breast surgeons.• Method is depend on shape of contralateral breast and chest wall.• Can be made either of a silicone implant or autologous material or both methods.• Indicated for; – < 55 yrs old – DCIS, LCIS & Stage I & II BC – pt who are undergoing prophylactic mastectomy
• Chemotherapy: – Cyclophosphamide, metrotrexate , 5-fluorouracil (CMF) = gold standard. – combination of chemotherapeutic agent containing doxorubicin can be used – Administration of chemotherapy ( 2/> agents) improves survival rate – Side effect: nausea, vomiting, myelosuppression, alopecia, thrombocytopenia, exercise intolerance 47
• Hormonal Therapy: Anti-estrogen: a. Tamoxifen – a non-steroidal anti-estrogenic compound that compete w/ estrogen at receptor site. – Estrogen receptor assay should be determined; if negative chance of success is very low 48
Mechanism of action of tamoxifen as an antitumor agentAnti-estrogen effects- blockage of estrogen receptor Local effects - independent of oestrogen receptor Decrease TGFα stromal cell + Increase TGFβ - 49
Aromatase inhibition within the breast tumour cell P-450 Aromatase tumour + NADPH-cytochrome P-450 reductase growth ANDROGENS OESTROGENS(Testosterone, (Oestradiol, oestrone)androstenedione,16-OH-testosterone) Aromatase Inhibitors 50
Therapeutic Approach for Breast CancerA. Carcinoma in Situ: 1. DCIS: a. Breast conserving surgery + radiation therapy w/ or w/o tamoxifen b. Total mastectomy w/ or w/o tamoxifen c. Breast-conserving surgery w/o radiation therapy 2. Lobular Carcinoma in Situ: a. Observation after diagnostic biopsy b. Tamoxifen to decrease the incidence of subsequent breast cancer c. Bilateral prophylactic total mastectomy, w/o axillary dissection 51
Follow - up• ALL pts with BC should be F/U• Objectives of F/U: – support & counselling – detect potentially curable conditions ( such as local recurrence of cancer in the breast following BCT & to detect new cancers in opposite breast) – manage pts in whom metastatic develops, & to determine outcome
• During F/U: – history, P/E – advise pt to do BSE monthly – annual mammography after therapy for primary BC – after BCT, the first mammogram should be performed 6 months after completion of radiotherapy