Breast Carcinoma

0
1296
    • Tumours suitable for breast conservation
      • Small single tumours in a large breast
      • Peripheral location
      • No local advancement or extensive nodal involvement
    • For tumours that are suitable for breast conservation there is no difference in local recurrence or overall survival when BCS + radiotherapy is compared to mastectomy (MCQ)
    • Aims of axillary surgery
      • 30-40% of patients with early breast cancer have nodal involvement
      • The aims of axillary surgery is to:
        • To eradicate local disease
        • To determine prognosis to guide adjuvant therapy
      • Clinical evaluation of the axilla is unreliable (30% false positive, 30% false negative)
      • No reliable imaging techniques available
      • Surgical evaluation important and should be considered for all patients with invasive cancer
    • Levels of axillary clearance are assessed relative to pectoralis minor (MCQ)
      • Level 1  -below pectoralis minor
      • Level 2 –upto upper border of pectoralis minor
      • Level 3 – to the outer border of the 1st rib
    • Axillary samplings removes at least four nodes (MCQ)
    • Pre-operative axillary ultrasound and biopsy may allow a tailored approach tthe axilla
    • Clinical points in favour of axillary clearance (MCQ)
      • Axillary clearance both stages and treats the axilla
      • Sampling potentially misses nodes and under stages the axilla
      • Surgical clearance possibly gains better local control
      • Avoids complications of axillary radiotherapy
      • Avoids morbidity of axillary recurrence
    • Clinical points in favour of axillary sampling(MCQ)
      • Only stages the axilla
      • Must be followed by axillary radiotherapy
      • The 60% of patients with node negative disease have unnecessary surgery
      • Radical lymphadenectomy in other cancers (e.g. melanoma) produces disappointing results
      • Avoids morbidity of axillary surgery
      • The combination of axillary clearance and radiotherapy is to be avoided
      • Produces unacceptable rate of lymphedema
    • Chronological prognostic factors
      • Age
        • Younger women have poorer prognosis of equivalent stage
      • Tumour size
        • Diameter of tumour correlates directly with survival
      • Lymph node status
        • Single best prognostic factor (MCQ)
        • Direct correlation between number and level of nodes involved and survival
      • Metastases
        • Distant metastases worsen survival
    • Some histological types associated with improved prognosis: (MCQ)
      • Tubular ,Cribriform ,Mucinous ,Papillary,Micro-invasive
      • Hormone and growth factor receptors (MCQ)
          • ER positivity predicts for response to endocrine manipulation (MCQ)
          • EGF receptors are negatively correlated with ER and poorer prognosis (MCQ)
      • Oncogenes
          • Tumours that express C-erb-B2 oncogene likely to be: (MCQ)
            • Resistant to CMF chemotherapy
            • Resistant to hormonal therapy
            • Respond to anthracycline
            • Respond to taxols
      • Proteases
          • Urokinase and cathepsin D found in breast cancer (MCQ)
          • Presence confers a poorer prognosis
      • Nottingham Prognostic Index (NPI) (MCQ)

      21

        • Post-operative adjuvant chemotherapy
          • Most commonly used regimen = CMF (MCQ)
            • Cyclophosphamide, Methotrexate, 5 Flurouracil
          • Given as six cycles at monthly intervals
          • No evidence that more than 6 months treatment is of benefit
          • Greatest benefit  seen in premenopausal women
          • High -dose chemotherapy with stem cell rescue produces no overall survival benefit

        22

          • Primary (neoadjuvant) chemotherapy
            • Chemotherapy prior to surgery for large or locally advanced tumours (MCQ)
            • Shrinks tumour often allowing breast conserving surgery rather than mastectomy
            • 70% tumours show a clinical response
            • In 20–30% this is response is complete
            • Surgery required even in those with complete clinical response
            • 80% of these patients still have histological evidence of tumour
            • Primary systemic therapy has not to date been shown to improve survival
          • Endocrine therapy in breast cancer
            • Tamoxifen(MCQ)
              • Tamoxifen is an oral anti-oestrogen
              • Effective in both the adjuvant setting and in advanced disease
              • 20 mg per day is as effective as higher doses
              • 5 years treatment is better than 2 years
              • Risk of contralateral breast cancer reduced by 40%
              • Greater benefit seen in oestrogen receptor rich tumours(MCQ)
              • Benefit still seen in oestrogen receptor negative tumours
              • Benefit observed in both pre and post menopausal women(MCQ)
              • Risks of Tamoxifen use(MCQ)
                • Uterine adenocarcinoma, sarcoma
                • Cataracts
                • DVT, PE
                • osteoporosis
                •  No change in incidence of heart disease
            • Aromatase inhibitors
                • Reduced the peripheral conversion of androgens to oestrogens
                • Only effective in post menopausal women(MCQ)
                • May be superior to tamoxifen(MCQ)
          • Locally advanced breast cancer
            • Regarded as a tumour that is not surgically resectable
            • Clinical features include:
                • Skin ulceration
                • Dermal infiltration
                • Erythema over the tumour
                • Satellite nodules
                • Peau d ‘orange
                • Fixation to chest wall,serratus anterior or intercostal muscles
                • Fixed axillary nodes
              • Strictly speaking, LABC includes: T3+N1 – 3 or T4+N0 – 3 or any T+N2 – 3 (i.e. Stage III A/B disease) (MCQ)
              • Management
                • If oestrogen receptor-positive usually treated with primary hormonal(MCQ)
                • If oestrogen receptor-negative chemotherapy may be useful (MCQ)
                • Radiotherapy may be useful in local control of disease
                • If adequate response a salvage mastectomy can be consider
            • Who gets chemotherapy?
              • Premenopausal: (MCQ)
                •  ER/PRNegative
                •  T>1cm
                •  Any N, including micro (SN+)
              • Postmenopausal (up to 90% are ER/PR+get tamoxifen): (MCQ)
                •  ER/PRNegative
                • T > 2 cm  ≥ 4 nodes OR matted nodes (regardless of ER/PR)
                • (Hence, ER/PR+, ≤ 3 unmatted nodes no chemo)
            • Who gets axillary radiation? (MCQ)
              • (In general, want to avoid axillary radiation following dissection)
              • Positive(+) supraclavicular node
              •  matted nodes (extracapsular extension)
              •  ≥ 4 nodes
            • Who gets breast irradiation? (MCQ)
              •  any segmental resection for invasive or DCIS
              •  inflammatory disease (T4/skin involvement); some T3
            • Chemotherapy/Hormonal* Treatment:
              • Premenopausal(MCQ)
                •  chemo for almost any tumor > 1 cm (regardless of nodal status)
                •  cytoxan & adriamycin
                •  add taxane if node positive
                •  tamoxifen if ER/PR positive
                • arimidex and aromatase inhibitors not effective in premenopausal since can’t compete with estrogen produced
              • Postmenopausal(MCQ)
                •  tamoxifen or arimidex if node negative and ER/PR+
                •  Chemo if poorly differentiated and > 1 cm (even if node negative)
                •  cytoxan & adriamycin ± taxane if node positive
                •  tamoxifen or adriamycin if elderly, node positive, and ER/PR+
              • Premalignant Lesions of breast
              • DCIS
                • Cell of originInner layer of epithelial cells in major ducts
                • Definition- Proliferation of ductal cells that spread through the ductal system but lack the ability to invade the basement membrane
                • Age> 1⁄2 of cases occur after menopause (MCQ)
                • Sometimes presents with palpable mass
                • Diagnosis – (MCQ)
                  • Clustered micro calcifications on mammogram
                  • malignant epithelial cells in breast duct on biopsy
                • Lymphatic invasion – < 1%
                • Risk of invasive cancer
                  • Increased risk in ipsilateral breast  (MCQ)
                  • usually same quadrant; (MCQ)
                  • infiltrating ductal carcinoma most common histologic type (MCQ)
                  • comedo type has the worst prognosis (MCQ)
                • Treatment  (MCQ)
                  • If small (<2cm): Lumpectomy with either close follow-up or radiation
                  • If large (>2cm): Lumpectomy with 1-cm margins and radiation
                  • If breast diffusely involved: Simple mastectomy
              • LCIS
                • Cell of origin  –Cells of terminal duct–lobular unit  (MCQ)
                • Definition- A multifocal proliferation of acinar and terminal ductal cells
                • Age- Vast majority of cases occur prior to menopause
                • Never presents with Palpable mass  (MCQ)
                • Diagnosis – Typically a clinically occult lesion; undetectable by mammogram and incidental on biopsy
                • Lymphatic invasion – Rare
                • Risk of invasive cancer (MCQ)
                  • Equally increased risk in either breast
                  • infiltrating ductal carcinoma also most common histologic type (you might have not expected this when asked in MD Entrance)
                  • associated with simulta- neous LCIS in the contralateral breast in over 1⁄2 of cases
                • Treatment (MCQ)
                  • None
                  • bilateral mastectomy an option if patient is high risk
              • Infiltrating Ductal Carcinoma
                • Most common invasive breast cancer (80% of cases). (MCQ)
                • Most common in perimenopausal and postmenopausal women. (MCQ)
                • Ductal cells invade stroma in various histologic forms described as scirrhous, medullary, comedo, colloid, papillary, or tubular.
                • Metastatic to axilla, bones, lungs, liver, brain.
              • Infiltrating Lobular Carcinoma
                • Second most common type of invasive breast cancer (10% of cases)
                • Originates from terminal duct cells  (MCQ)
                • like LCIS, has a high likelihood of being bilateral (MCQ)
                • Presents as an ill-defined thickening of the breast
                • Like LCIS, lacks microcalcifications (MCQ)
                • often multicentric (MCQ)
                • Tends to metastasize to the axilla, meninges, and serosal surfaces
              • Paget’s Disease (of the Nipple)
                • 2% of all invasive breast cancers
                • Usually associated with underlying LCIS or ductal carcinoma extending within the epithelium of main excretory ducts to skin of nipple and areola  (MCQ)
                • Presentation:
                  • Tender, itchy nipple with or without a bloody discharge with or without a subareolar palpable mass (MCQ)
                • Treatment: Usually requires a modified radical mastectomy (MCQ)
              • Inflammatory Carcinoma
                • Two to 3% of all invasive breast cancers.
                • Most lethal breast cancer.
                • Vascular and lymphatic invasion commonly seen at pathologic evaluation.
                • Frequently presents as erythema, “peau d’orange,” and nipple retraction. (MCQ)
                • Treatment:
                  • Consists of chemotherapy followed by surgery and/or radiation, depending on response to chemotherapy. (MCQ)
              • BREAST CANCER
                • One in eight women will develop breast cancer in their lifetime.
                • Incidence increases with increasing age.
                • One percent of breast cancers occur in men.
                • Risk Factors  (MCQ)
                  • Early menarche (< 12) (MCQ)
                  • Late menopause (> 55) (MCQ)
                  • Nulliparity or first pregnancy > 30 years
                  • Old age
                  • History of breast cancer in mother or sister
                  • especially if bilateral or premenopausal
                  • Genetic predisposition
                    • BRCA1 or BRCA2 positive
                    • Li–Fraumeni syndrome
                  • Prior personal history of breast cancer
                  • Previous breast biopsy
                  • DCIS or LCIS
                  • Atypical ductal or lobular hyperplasia
                  • Postmenopausal estrogen replacement (unopposed by progesterone) (MCQ)
                  • Radiation exposure
              • Breast Cancer in Pregnant and Lactating Women
                • 3  breast cancers are diagnosed per 10,000 pregnancies.
                • A FNA should be performed.
                • If it identifies a solid mass, then it should be followed by biopsy.
                • Mammography is possible as long as proper shielding is used.
                • Radiation is not advisable for the pregnant woman. (MCQ)
                • For stage I or II cancer, a modified radical mastectomy should be done rather than a lumpectomy with axillary node dissection and postoperative radiation. (MCQ)
                • If lymph nodes are positive, delay chemotherapy until the second trimester. (MCQ)
                • Suppress lactation after delivery.
              • Breast Cancer in Males
                • Predisposing factors: (MCQ)
                  • Klinefelter’s syndrome
                  • estrogen therapy
                  • elevated endogenous estrogen
                  • previous irradiation
                  • trauma.
                • Infiltrating ductal carcinoma most common histologic type (men lack breast lobules). (MCQ)
                • Diagnosis tends to be late, when the patient presents with a mass, nipple retraction, and skin changes.
                • Stage by stage, survival is the same as it is in women.
                • However, more men are diagnosed at a later stage.
                • Treatment for early-stage cancer involves a modified radical mastectomy and postoperative radiation. (MCQ)
              • Genetic Predisposition
                • Five to 10% of breast cancers are associated with an inherited mutation.
                • p53
                  • A tumor suppressor gene
                  • Li–Fraumeni syndrome results from a p53 mutation.
                • BRCA1  (MCQ)
                  • On 17q21, also associated with ovarian cancer.
                • BRCA2  (MCQ)
                  • On chromosome 13
                  • not associated with ovarian cancer.
                • Somatic mutation of p53 in 50% and of Rb in 20% of breast cancers.
              • Screening Recommendations (from the American Cancer Society)
                • Screening reduces mortality by 30–40%.
                • Begin monthly breast self-examinations at age 20. (MCQ)
                • First screening mammogram at age 35. (MCQ)
                • Annual mammograms after age 50.
              • Diagnostic Options
                • Mammography
                  • Identifies 5 cancers/1,000 women.
                  • Sensitivity 85–90%.
                  • False positive 10%, false negative 6–8%.
                  • If cancer is first detected by mammogram, 80% have negative lymph nodes (vs. 45% when detected clinically). (MCQ)
                  • Suspicious Findings (MCQ)
                    • Stellate, speculated mass with associated microcalcifications
                  • Reporting Mammogram Results
                    • I: No abnormality
                    • II: Benign abnormality
                    • III: Probably benign finding
                    • IV: Suspicious for cancer
                    • V: Highly suspicious for cancer
                • Ultrasound
                  • Advantages
                    • No ionizing radiation
                    • Good for identifying cystic disease and can also assist in therapeutic aspiration
                    • Results easily reproducible
                  • Disadvantages (MCQ)
                    • Resolution inferior to mammogram
                    • Will not identify lesions < 1 cm
                • FNA (Aspiration of Tumor Cells with Small-Gauge Needle)
                  • Advantages
                    • Low morbidity
                    • Cheap
                    • Only 1–2% false-positive rate
                  • Disadvantages  (MCQ)
                    • False-negative rate up to 10%
                    • Requires a skilled pathologist
                    • May miss deep masses
                • Needle Localization Biopsy
                  • Locates occult cancer in > 90%
                • Core Biopsy
                  • Has chance of sampling error
                • Stereotactic Core Biopsy
                  • Advantages
                    • Fewer complications compared to needle localization biopsy
                    • Less chance of sampling error than core biopsy alone
                    • No breast deformity
                • Treatment Decisions
                  • Types of Operations
                    • Radical mastectomy (MCQ)
                      • Resection of all breast tissue, axillary nodes, and pectoralis major and minor muscles (rarely preferred)
                    • Modified radical mastectomy: (MCQ)
                      • Same as radical mastectomy except pectoralis muscles left intact
                    • Simple mastectomy: (MCQ)
                      • Same as radical mastectomy except pectoralis muscles left intact and no axillary node dissection
                    • Lumpectomy and axillary node dissection: (MCQ)
                      • Resection of mass with rim of normal tissue and axillary node dissection—good cosmetic result
                    • Sentinel node biopsy: (MCQ)
                      • Recently developed alternative to complete axillary node dissection:
                      • Based on the principle that metastatic tumor cells migrate in an orderly fashion to first draining lymph node(s).
                      • Lymph nodes are identified on preoperative scintigraphy and blue dye is injected in the periareolar area.
                      • Axilla is opened and inspected for blue and/or “hot” nodes identified by a gamma probe. (MCQ)
                      • When sentinel node(s) is positive, an axillary dissection is completed.
                      • When sentinel node(s) is negative, axillary dissection is not performed unless axillary lymphadenopathy identified.
              • TNM System for Breast Cancer  (MCQ)
                • Tx: Cannot assess primary tumor
                • T0: No evidence of primary tumor
                • T1: < 2 cm
                • T2: < 5 cm
                • T3: > 5 cm
                • T4: Any size, with direct extension to chest wall or with skin edema or ulceration
                • Nx: Cannot assess lymph nodes
                • N0: No nodal mets
                • N1: Movable ipsilateral axillary nodes
                • N2: Fixed ipsilateral axillary nodes
                • N3: Ipsilateral internal mammary nodes
                • Mx: Cannot assess mets
                • M0: No mets
                • M1: Distant mets or supraclavicular nodes
              • Staging System for Breast Cancer and 5-Year Survival Rates
                • Stage 0 -DCIS or LCIS (MCQ)
                • Stage I-  (MCQ)
                  • Invasive carcinoma < 2 cm in size (including carcinoma in situ with mi- croinvasion) without nodal involvement and no distant metastases.
                • Stage II-  (MCQ)
                  • Invasive carcinoma < 5 cm in size with involved but movable axillary nodes and no distant metastases
                  • a tumor > 5 cm without nodal involvement or distant metastases
                • Stage III – (MCQ)
                  • Breast cancers > 5 cm in size with nodal involvement
                  • any breast cancer with fixed axillary nodes
                  • any breast cancer with involvement of the ipsilateral internal mammary lymph nodes
                  • any breast cancer with skin involvement, pectoral and chest wall fixation, edema
                  • clinical inflammatory carcinoma, if distant metastases are absent
                • Stage IV – (MCQ)
                  • Any form of breast cancer with distant metastases (including ipsilateral supraclavicular lymph nodes)
              • Hormone Receptor Status and Response to Therapy
                • Hormone Receptor Status vs Response to Therapy
                  • ER+/PR+ –80%
                  • ER/PR+ –45%
                  • ER+/PR35%
                  • ER/PR10%
                • Hormonal Therapy: Tamoxifen
                • Selective estrogen receptor modulator  (MCQ)
                  • blocks the uptake of estrogen by target tissues
                • Side effects: (MCQ)
                  • Hot flashes, irregular menses
                  • thromboembolism,
                  • increased risk for endometrial cancer
                • Survival benefit for pre- and postmenopausal women, but benefit greater for ER+ patients
                • May get additional benefit by combining tamoxifen with chemotherapy
              • Recurrence
                • 5–10% local recurrence at 10 years
                • Metastases in < 10% of cases
                • Local chest wall recurrence most common within 2 to 3 years, if at all
              • Metastasis
                • Median survival 2 years.
                • Palliative therapy indicated.
                • Doxorubicin in this setting has a response rate of 50% with a 1-year survival of 60%.
              • Clinical Pearls:
                • Tumors with high tendency to metastise to Bone – Thyroid ,Renal ,Lung ,Prostate ,Breast
                • Twenty percent of infiltrating lobular breast carcinoma have simultaneous contralateral breast cancer. (MCQ)
                • Typical Clinical scenario:
                  • A 70- year-old female presents with a pruritic, scaly rash of her nipple–areolar complex and a bloody nipple discharge.
                  • Diagnosis :  Paget’s disease. (MCQ)
                  • Biopsy and pathologic exam required to confirm diagnosis.
                • Typical Clinical scenario:
                  • A 49- year-old female presents with enlargement of her left breast with nipple retraction, erythema, warmth, and induration. (MCQ)
                  • Diagnosis :  Inflammatory breast carcinoma.
                  • Fibrocystic changes of the breast alone is not a risk factor for breast cancer. (MCQ)
                  • Despite all known risk factors, most women with breast cancer (75%) present without any identifiable risk factors.
                  • Termination of pregnancy is not part of the treatment plan for breast cancer and does not improve survival.
                  • Males with breast cancer often have direct extension to the chest wall at diagnosis.
                  • Genetic syndromes associated with breast cancer:
                    • Autosomal dominant: (MCQ)
                        • Li–Fraumeni
                        • Muir–Torre
                        •  BRCA1and BRCA2
                        • Cowden’s syndrome
                        •  Peutz–Jeghers syndrome
                      • Autosomal recessive: (MCQ)
                          • Ataxia–telangiectasia
                            • Start yearly mammograms 10 years before the age at which first-degree relative was diagnosed with breast cancer. (MCQ)
                            • Benign cysts should not be bloody. A bloody aspirate usually indicates malignancy.
                            • Five to 10% of palpable masses have a negative mammogram  (MCQ)
                            • Mammography is more useful if age 30 because the large proportion of fibrous tissue in younger women’s breasts make mammograms more difficult to interpret.
                            • Recommended chemotherapy for breast cancer is  (MCQ)
                              • CAF (cyclophosphamide, adriamycin, 5-FU)
                              • CMF (methotrexate instead of adriamycin).
                            • Prognosis depends more on stage than on histologic type of breast cancer.
                            • Lumpectomy with postoperative radiation is a viable treatment option only in stages I and II (MCQ)

                     


                Breast Cancer
                This 3D medical animation outlines the progression of breast cancer and describes the stage classifications based on the extent of the disease.
                Understanding Pathology for Breast Cancer
                Dr. Sean Thornton, a pathologist with Cellnetix Laboratories and Pathology, talks about the pathology and biology of breast cancer and the role a pathologist plays in your care.
                Breast cancer – Symptoms and treatment
                Breast cancer is the most common form of cancer in women. In this animation we explain what cancer is and how it can develop in the breasts. Furthermore, we describe the different symptoms that are possible signs for breast cancer and the risk factors associated with this disease. Furthermore, we name the different types of breast screening methods (such as mammography) and the treatment options that are available.

                Healthchannel makes complex medical information easy to understand. With 2D and 3D animations checked by medical specialists, we give information on certain diseases: what is it, what are the causes and how is it treated? Subscribe to our Youtube channel and learn more about your health!
                Histopathology Breast –Ductal carcinoma
                Histopathology Breast –Ductal carcinoma
                Breast Cancer Pathogenesis
                The pathogenesis of Breast Cancer explained in details.
                Breast Cancer Lumpectomy and Sentinel Lymph Node Biopsy, Darrin Hansen MD, Salt Lake City Utah
                A narrated breast lumpectomy and sentinel lymph node biopsy procedure for breast cancer
                Breast Cancer Surgery
                This 3D patient education medical animation depicts various surgical procedures to remove breast cancer lumps and tumors. The surgeries include lumpectomy, simple mastectomy, modified radical mastectomy, and radical mastectomy surgery.
                Breast Cancer Surgery and Recovery
                Documenting the physical aspects of breast cancer – from biopsy through reconstruction surgery.
                Clinical Anatomy – Breast Cancer
                This video introduces the relevant anatomy and pathology underpinning the modern treatment of breast cancer.