Angelic_doc - Breast Cancer

Breast Cancer # Cancer Breast Patients at KAUH: < 60 YO  85.1 % < 50 YO  64.5 % < 40 YO  30.6 % # Incidence: 12% life time risk # Introduction:       

Monoclonal Average doubling time = 100 days One cell  1 cm lump in 8 – 10 years At 2nd or 3rd year  Hematogenous & lymphatic invasion by cancer cells Women die from breast cancer because of metastasis Local surgical treatment to control local disease & may prevent further metastasis Systemic treatment should be considered in all

# Risk factors: Major:          

Age (elderly) female (100 x male risk) Family Hx (especially: young, bilateral, more than 1 relative) Cancer breast in other side (more common in < 50 YO, lobular)  1 - 3% synchronous contralateral cancer , 5 – 8 % metachronous bilateral breast CA Carcinoma in situ Prior lumpectomy [of breast] Atypical epithelial hyperplasia  4 x risk Hyperplasia (moderate/florid)  2 x risk DCIS , LCIS Mutation of the major breast cancer susceptibility inherited genes (BRCA I & II)  very IMPortant (easy: BR = Breat Cancer, CA = cancer)

Minor:        

Nulliparous 1st pregnancy after age of 30 - 35 Early menarche < 12 – 13 YO late menopause > 51 - 55 YO OCP, HRT for 10 years  1 – 1.5 relative risk Diet (↑ fat & alcohol) Endometrial Ca Obese

 

Radiation No breast feeding

NOTE: fibrocystic disease is NOT a risk factor for breast cancer # Common signs & symptoms: 1. 2. 3. 4. 5. 6. 7. 8.

No symptoms  Palpable mass most are painless Nipple discharge (Intraductal papilloma is the most common cause of bloody nipple discharge in young woman) Nipple rash\retraction Skin changes (dimples)  skin retraction occurs due to tumor involvement of Cooper's ligaments and subsequent traction on ligaments pull skin inward Local edema Palpable axillary/supraclavicular lymph nodes

# Clinical Presentation:  

Most common site: UOQ (50%), Lt Breast Ill defined, hard, fixed, lump in the breast

# Hx of metastasis in Breast Ca:     

Brain  projectile vomiting WITHOUT nausea, headache, seizures Lung  cough (early), hemoptysis Liver  RUQ pain, Jaundice Bone  Pain Wt loss

NOTE: Lymph nodes are the most common site of metastasis, & Bone is the most common site for "distant" metastasis # TNM staging: (T) 0  no primary tumor IS  in situ (DCIS, LCIS), Paget's sisease WITHOUT tumor 1  less than 1 cm 2  2 – 5 cm 3  more than 5 4  Peau D'Orange (orange peel)  the appearance of the edema of dermis in inflammatory carcinoma of the breast

(N) 0  no LN metastasis 1  ipsilateral axillary LN  movable 2  ipsilateral axillary LN  fixed 3  ipsilateral intramummary LN 4  ipsilateral supraclavicular  which is distant metastasis (M) 0  no distant metastasis 1  distant metastasis [skeletal (most common) especially lumbar, liver, lung, brain, others] # Staging: Stage 0 I

1 A

2

B

3

A

(Total N = 2)

II

III

(Total N = 3) B 7 (Total T = 4) IV

T N M

Total TNM TIS N0 M0 T1 N0 M0 T1 N1 M0 T3 N0 M0 T any N2 M0 T any N3 M0 T4 N any M0

Whenever there is metastasis (M = 1)

Survival rate 95% 85% T2 N0 M0 T2 N1 M0

70% 60% 55%

30%

5 – 10 %

# Screening: a. Breast Self Exam (BSE)  At 20 YO, monthly , best time: 7 – 8 days (1 week) after menstrual period

b. Physical examination (by physician)   

20 – 40 YO: Q 2 – 3 years >40 YO: annually

c. Mammography   

40 - 50 YO: Q 1 – 2 years (every year, or every other year) > 50 YO: annually (maximum benefit from age 50 – 69 YO)

# Diagnosis (work up for a breast mass): [1] Clinical breast Exam [2] breast Ultrasound / Mammogram:  

Younger age (less than 35 YO)  do US, as they have more fibrous tissue, which makes mammograms harder to interpret. Those over 35 YO  mammogram, as breast tissue undergoes fatty replacement with age, making masses more visible.

 US: When you do an US  It will tell if it's cystic or solid: If it's cystic  do FNA (fine needle aspiration)  see: o o o

If the mass disappears after aspiration  That's fine (fibrocystic disease)  Follow Up (F/U) If it's bloody (increased vasularity: indicate CA) do biopsy Cytology is done for nipple discharge, but not routinely done for breast cystic fluid; bloody fluid should be sent for cytology

If it's solid  excise  Mammography: Radiological Classification [Breast Imaging Reporting & Data System (BI-RADS) Catergory]: 0  need additional imaging evaluation 1  negative 2  benign finding 3  probably benign finding  6 months follow up 4  suspicious abnormality  consider biopsy 5  highly suggestive of malignancy  appropriate action should be taken 6  known (biopsy proven) malignancy  treat

Signs in mammogram suggestive of malignancy? 1) 2) 3) 4) 5) 6)

Irregular / Spiculated mass (classic picture of breast cancer on mammogram) Distortion of breast architecture Asymmetrical fibrosis Microcalcephications Increased vascularity Skin thickening / skin edema

NOTEs:  

The mammogram is obtained 1st before biopsy, as tissue extraction (core or open) may alter the mammographic findings. FNA may be done prior to the mammogram b'coz the FN usually will not affect the mammographic findings.

[3] Biopsy: Indications of Biopsy: -

Persistent mass after aspiration Solid mass Blood in cyst aspirate Suspicious lesion by mammography/US/MRI Bloody nipple discharge Ulcer or dermatitis of nipple Patient's concern of persistent breast anomaly

Types of Biopsy: 1) 2) 3) 4) 5)

Open incisional biopsy True cut (open excisional) biopsy  most reliable Core needle biopsy Mammographic localization needle biopsy Mammotome biopsy (computerized stereotactic imaging-guided needle biopsy)

Proceed to open biopsy of breast cyst in case of: -

Second cyst recurrence Bloody fluid in the cyst Palpable mass after aspiration

What you need to Do?  Hormone receptor assay (immune-histo-chemistry): Check for estrogen (ER) & progesterone (PR) & HER-2 (human epidermal growth factor 2) receptors in the biopsy specimen

 Pathological Classification (Grading): 1) Non-invasive:  Carcinoma In Situ o DCIS (Ductal Carcinoma In Situ), aka Intraductal Carcinoma  cancer cells in the ducts without invasion .. (Age: same as invasive CA) o LCIS (Lobular Carcinoma In Situ)  carcinoma cells in the lobules of the breast without invasion .. (Age: > 50 % premenopausal) Incidence: 2 -3 % of all breast Ca Axillary LNs are rare (less than 2%, usually when microinvasion is seen with DCIS), so LN dissection is not required Diagnosis

DCIS

LCIS

Cluster of microcalcifications on mammogram (80%) , nonpalpable mass. Core or open biopsy  histologic , cytological factors, nuclear geade, presence or absence of necrosis. The most aggressive histologic type is Comedo (necrosis).

Found incidentally on biopsy, no mammographic findings (occult), no lump (never)

Multicentricity

35 %.

& bilateral (60 – 80 %)

Treatment (NSABP B-17, B24) - breast conservation - lumpectomy +/RT if ≥ 1 cm clear margin - if close or +ve margin  skin sparing mastectomy or simple mastectomy +/reconstruction + tamoxifen - axillary LN dissection & systemic therapy is NOT indicated. - close observation (physical exam every 6 – 12 months & annual mammograms, monthly BSE) - consider prophylactic tamoxifen 10 mg BID for 5 years OR - bilateral, prophylactic simple mastectomy w/ or w/out reconstruction as the marker lesion in itself may not be dangerous.

Transformation to Beast CA incidence Type Which breast 40 – 60 % Ductal Ipsilateral

 considered premalignant lesion, if untreated  potentially fatal invasive cancer: Subsequent development of infiltrating ductal carcinoma (30%) in the same breast (Cancer arises Directly in the ipsilateral breast)

20 %

Ductal

Bilateral

 considered a marker for ↑ risk of invasive CA: Equal risk of invasive carcinoma in both breasts (LCIS is a risk marker for future development of cancer in either breast). About 30% of women with LCIS develop invasive breast CA in the 20 years after diagnosis. Most common type, infiltrating ductal carcinoma, with equal distribution in the contralateral & ipsilateral breasts.

2) Invasive: [atypical hyperplasia on mammotome biopsy] 1. Ductal  5 subtypes:  Medullary  Colloid  Tubular  Papillary  Scirrhous 2. Lobular 3. Paget's: Scaling Rash / Dermatitis (Itching or burning) of the nipple (caused by invasion of skin by cells from a ductal carcinoma), superficial erosions or ulceration of the skin +/- mass  underlying invasive ductal CA in X % Treatment: mastectomy or excision of nipple-areolar complex if limited to retroareolar area 4. Inflammatory: The most malignant form of breast CA. metastasis is common at time of diagnosis. C/P: rapidly growing, diffusely enlarged breast. Skin is erythematous, edematous & warm. NO mass. Dx: redness of 1/3 of breast skin + biopsy shows invasion of subdermal lymphatics. Suspect it if: "MASTITIS" doesn't clear up in 1 – 2 weeks with antibiotics  do biopsy. Treatment: Chemotherapy 1st..!! Then often followed by radiation, mastectomy, or both.  Histological Grading:  NOTE: It's old & not used currently Grade 1: well differentiated breast cells; cells generally appear normal Grade 2: moderately differentiated breast cells have characteristics between grade 1 and grade 3 tumor Grade 3: poorly differentiated breast cells # Investigations: a. All patients must be tested for: 1. LFT especially ALP 2. CXR b. Symptomatic / previously test +ve : 1. Brain CT (headache, vomiting) 2. Chest CT (nodule on CXR) 3. Abdomen CT (↑ ALP, jaundice) 4. Bone scan (bone pain, ↑ ALP) # Management:  Pre-operative evaluation of patients with primary operable breast CA: 

Complete Hx & physical Ex

   

Bilateral mammography (cancer in one breast is a risk factor for cancer in the contralateral breast). Chest radiograph (CXR) to check for lung metastasis LFTs to check for liver metastasis Further studies only when indicated by symptoms.

 Prognostic factors: May be at higher risk to develop metastasis High risk group (many +ve factors) may benefit from systemic therapy Proven factors:    

Tumor size Axillary lymph node status Estrogen & progesterone receptor status (ER & PR) Human epidermal growth factor receptor (HER-2 / neu)

Questionable value:      

Breast mucin marker (CA 15-3, CA 549, CAM 26, CAM 29) CEA Mutation of tumor suppressor gene TP 53 (P53) S-phase fraction Ki-67 antibody Thymidine labeling indix (mitotic indix)

 Choice of management depend on: 1. Stage (more mportant than grade) 2. Histologic grade 3. Hormone receptor assay  General Guidelines:  Hormonal therapy: Check estrogen, progesterone (ER & PR) & HER-2 receptor status of the biopsy in all patients using immune-histochemistry  affects the response to hormonal therapy ER PR

+ve 60 % response 80 % response

-ve < 5%

+ve ER may carry a better prognosis. Available treatments: 1. Tamoxifen: in pre- & post- menopausal. 10 mg twice daily for at least 2 years.

SFx : -

Endometrial CA (2.5 relative indix) DVT, pulmonary embolism Cataract Hot flushes Mood swings

NOTE: if chemotherapy is used, Tamoxifen is started AFTER the completion of chemo. 2. Aromatase inhibitors (e.g. Letrozole) : used as second line treatment in postmenopausal patients (only) failing hormonal treatment. If HER-2 is strongly +ve (score +3), Herceptin (trastuzumab) [monoclonal antibody IV] can be given. 25% of CA breast over express HER-2. These tumors grow faster & recurs more than HER-2 –ve. SFx: - Fever +/- chills - Weakness, nausea, vomiting, … - Cardiac & respiratory failure  Types of Breast Surgery (Mastectomy):  Subcutaneous: removal of breast tissue, spares nipple-areolar complex, skin & nodes. NOT a CA operation.  Partial: Removal of part of the breast; e.g. lumpectomy  Total (Simple): removal of the whole breast  Radical: removal of the breast tissue + axillary LNs + underlying pectoralis muscle. (rare to be done)  Modified Radical Mastectomy (MRM): removal of the entire breast + axillary LNs but not muscle  Chemotherapy:  Types: - CMF: cyclophosphamide, methotrexate (MTX), 5-fluorouracil (5FU)  used to be 1st line - CAM: cyclophosphamide, Adriamycin, 5-fluorouracil (5FU) - Taxotere (Taxol)  1st line now  Indications: A. Neoadjuvant chemotherapy (before Sx): Taxane (paclitaxel / Docetaxel) + Doxorubicin given preoperatively to down stage the cancer. B. Adjuvant chemotherapy (after Sx): Given postopearatively to kill residual tumor & eliminate microscopic mets. C. Rx of metastasis to liver, lung, brain  Management of breast cancer according to stage: In all stages, if receptor +ve  give hormonal therapy

[1] stage I & II: We have 2 options (MRM or BCT) + chemo if LN +ve, high grade (poorly differentiated), or invasion of lymphatics: a) Modified radical mastectomy (MRM): Remove everything with sparing of pectoralis major muscle. b) Breast conservative therapy (BCT): Lumpectomy with negative margins + axillary LN dissection or sentinel LN(s) (SNL) biopsy + irradiation to breast  in the OR  we do lumpectomy. Then ask the pathologist for frozen section to see if the margins of breast are diseased or not. If it's –ve [no disease]  map out the sentinel LN (1st regional set of LNs to receive the tumor cells; primary draining LNs) by injecting the breast with a dye (methylene blue or technetium-labeled sulfur colloid). If the dye was taken by 1st LN in the breast, it means that the LNs are diseased  remove them all (dissection). Then, 2 weeks later start Radiotherapy. 



SNL –ve: - No further axillary dissection  - False –ve is negligible - Little risk of axillary failure in SNL-ve patients with no axillary dissection SNL +ve: - Complete axillary dissection or NOT..!!  Ongoing observation vs axillary dissection. - Axillary dissection is necessary if: 1. Significant probability of additional tumor bearing nodes (+ve nodes). 2. Axillary dissection has therapeutic value.

 BCT in Saudi Arabia is done in 15.7% patients, WHY? (USA = 45.7%) - Late Presentation - No standard Protocols for treatment - Neoadjuvant chemotherapy is stage III is not widely used  Relative contraindications of BCT: - Large mass in small sized breast - Subareolar tumor - Multifocal tumor  How do you choose: MRM or BCT? 1. Factors favoring BCT: - Patient preference - Tumor location & size are favorable for anesthetic result - Unifocal tumor - High risk for general anesthesia

2. Factors favoring MRM: - Patient preference - Multifocal tumor - Difficulty with follow-up anticipated - Inability to achieve –ve margin at lumpectomy - Large mass in small sized breast (no cosmetic advantage) - Contraindication to radiotherapy: o Pregnancy  major contraindication o Previous radiation to the chest o Collagen vascular disease; like scleroderma  Potential complications after MRM: - Ipsilateral arm lymphedema - Infection - Injury to nerves - Skin falp necrosis - Hematoma / seroma - Phantom breast syndrome [2] stage III: Down staging using neoadjuvant chemotherapy then treat as stage I & II. [3] stage 4: Palliative treatment (10 – 20 %). Mainly hormonal +/- chemo, radio, mastectomy.  Breast reconstruction: It doesn't prevent the diagnosis of recurrence. (see Mont Reid) 1. Prosthetic Implant between pectoralis minor & major. Usually, saline filled. Also, silicon. 2. TRAM flap  Transverse Rectus Abdominis Myocutaneous flap (see Surgical Recall page 379, 4th Edition) 3. Latissimus dorsi flap 4. Other flaps # Follow-Up: Metastasis occurs most frequently within the 1st 3 years, & risk ↑ with +ve LN involvement: A. Physical Ex: Q6 months for 3 years, Q 6 – 12 months for 2 years, Q 12 months forever. B. BSE: monthly C. Mammogram: annual

# Recurrence: Factors associated with high risk of recurrence: 1. 2. 3. 4. 5.

Young age ( < 35 YO) Tumor > 2 cm (stage II) Poor histologic grade –ve ER & PR Over expression of HER-2

Best of Luck… 

angelic_doc Sources: (Dr. Hassan Moria) Kia Ora's summary sheet 2008 – DiDi's sheet (Current & Browse Text Books) – Surgical Recall – Prof. Adnan Merdad's Lecture 2006 – Dr. Mohammed Gogandy's "IMPORTANT POINTS in The Surgical Clinical Exam" 2007-2008.