Breast Cancer

Diagnostic, Therapy, Pre-operative and Post-operative CareDr. Isa Basuki

Department of Surgery, AWS General Hospital

Introduction

•Breast cancer is a heterogeneous disease with a varying propensity for spread.•The disease tends to be slow growing, with pre-invasive phases that may extend over a number of years.•Breast cancer may recur many years after surgery, indicating the need for prolonged monitoring

Risk Factors• Cannot be Modified

• Increasing age• Female gender• Menstrual factors• Early age at menarche (onset of menses prior to age 12 yr)• Older age at menopause (onset beyond age 55 yr)• Nulliparity• Family history of breast cancer• Genetic predisposition (BRCA1 and BRCA2 mutation carriers)• Personal history of breast cancer• Race, ethnicity (white women have increased risk compared with

others)• History of radiation exposure

Cont’d• Could be modified• Reproductive factors• Age at first live birth (full-term pregnancy after age 30 yr)• Parity• Lack of breast-feeding• Obesity• Alcohol consumption• Tobacco smoking• Use of hormone replacement therapy• Decreased physical activity• Shift work (night shifts)

Results: Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to 1.28).

Conclusion: The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer

 Statistically significant associations were observed between breast cancer and work durations of ≥5 years with ≥6 consecutive night shifts, with the highest risk observed for progesterone receptor–positive tumors (odds ratio = 2.4, 95% confidence interval: 1.3, 4.3; P-trend = 0.01)

Epidemiology• In 2010, a total of 209,060 cases of invasive breast cancer

and almost 54,010 cases of in situ breast cancer were diagnosed in the United States• Approximately 40,000 deaths caused by breast cancer

annually• More than 1 million cases of breast cancer diagnosed

worldwide each year• The overall incidence of breast cancer was rising until

approximately 1999 because of increases in the average life span, lifestyle changes that increase the risk for breast cancer, and improved survival from other diseases.

Pathology• Noninvasive Breast Cancer

• Lobular Carcinoma in situ (LCIS)• Ductal Carcinoma in situ (DCIS)

• Invasive Breast Cancer• Invasive lobular carcinoma (10%)• Invasive ductal carcinoma

• Invasive ductal carcinoma, NOS (50%-70%)

• Tubular carcinoma (2%-3%)• Mucinous or colloid carcinoma (2%-

3%)• Medullary carcinoma (5%)• Invasive cribriform carcinoma (1%-3%)• Invasive papillary carcinoma (1%-2%)• Adenoid cystic carcinoma (1%)• Metaplastic carcinoma (1%)

• Mixed Connective and Epithelial Tumors• Phyllodes tumors, benign

and malignant• Carcinosarcoma• Angiosarcoma• Adenocarcinoma

Diagnosis• Patient History• Age • Reproductive history:

• Age at menarche• Age at menopause• History of pregnancies age at first full-term pregnancy

• Previous history of breast biopsies including the pathologic findings• If the patient has had a hysterectomy determine whether

the ovaries were removed• In premenopausal women recent history of pregnancy and

lactation

Cont’d• Patient History

• History of any use of long standing HRT or hormones used for contraception

• Family history Family Clustering Breast Cancer and Hereditary Breast Cancer, BRCA1 and BRCA2 mutation

• Specific breast complaint: • History of a mass• Breast pain• Nipple discharge• Sattelite nodules• Any skin changes

• If a mass is present:• How long it has been• Whether it changes with the menstrual cycle

Cont’d• Patient History

• If a cancer diagnosis is suspected:• Bone pain• Weight loss• Chronic cough • Respiratory changes

• Physical Examination:• Patient in the upright sitting position• Careful visual inspection for obvious masses, asymmetries, and skin

changes• The nipples are inspected and compared for the presence of retraction,

nipple inversion, or excoriation of the superficial epidermis

Cont’d• Physical Examination• Simple maneuvers such as stretching the arms high above

the head may accentuate asymmetries and dimpling• Edema of the skin produces a clinical sign peau d’orange• Combined with tenderness, warmth and swelling of the

breast hallmark of inflammatory carcinoma• When the primary tumor is located in the subareolar position

may result in retraction of the nipple• The patient is still in the sitting position, the examiner

supports the patient’s arm and palpates each axilla to detect the presence of enlarged axillary lymph nodes

Inspection of the breast in the upright position with the patient’s arms to the side (A), in the air (B), and hands on hips (C). (From Bland KI, Copeland EM III. The breast, 3rd ed. Philadelphia: WB Saunders,2004.)

Examination of the cervical (A), supraclavicular (B), and axillary nodes (C). (From Bland KI, Copeland EM III. The breast, 3rd ed. Philadelphia: WB Saunders, 2004.)

Cont’d• Physical Examination• The supraclavicular and infraclavicular spaces are similarly

palpated for enlarged nodes• The patient lying supine with the arm stretched above the

head.• The breast is best examined with compression of the tissue

toward the chest wall, with palpation of each quadrant and the tissue under the nipple-areolar complex• Palpable masses are characterized according to their size,

shape, consistency, and location and whether they are fixed to the skin or underlying musculature

Cont’d• Biopsy

Breast Imaging• Screening Mammography• Performed in asymptomatic women with the goal of

detecting breast cancer that is not yet clinically evident• At present, the American Cancer Society continues to

recommend annual screening mammography for women older than 40 years

• Ultrasonography• Useful in determining whether a lesion detected by

mammography is solid or cystic• Highly dependent on the operator

Cont’d• Magnetic Resonance Imaging

• useful for identifying the primary tumor in the breast in patients who present with axillary lymph node metastases without mammographic evidence of a primary breast tumor (unknown primary)

• May also be useful for assessing the extent of the primary tumor, particularly in young women with dense breast tissue

• Some surgeons to determine eligibility for breast conservation

• a screening tool in patients with known BRCA gene mutations and for detecting contralateral breast cancers in women diagnosed with a unilateral cancer on mammography

A, Stellate mass in the breast. The combination of a densitywith spiculated borders and distortion of surrounding breast architecture suggests a malignancy

B, Clustered microcalcifications. Fine, pleomorphic,and linear calcifications that cluster together suggest the diagnosis of ductal carcinoma in situ

C, Ultrasound image of breast cancer.The mass is solid, contains internal echoes, and displays an irregular border. Most malignant lesions are taller than they are wide

D, Ultrasound image of a simple cyst. By ultrasound, the cyst is round with smooth borders, there is a paucity of internal sound echoes, and there is increased through-transmission of sound, with enhanced posterior echoes

E, Breast MRI showing gadolinium enhancement of a breast cancer. Rapid and intense gadolinium enhancement reflects increased tumor vascularity. Lesion contour and size may also be assessed by MRI .

STAGING OF BREAST CANCERPrimary Tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

Tis (DCIS ) Ductal carcinoma in situ

Tis (LCIS ) Lobular carcinoma in situ

Tis (Paget’s) Paget’s disease of the nipple not associated with invasive carcinoma or carcinoma in situ (DCIS and/or LCIS ) in the underlying breast parenchyma.

T1 Tumor ≤20 mm in greatest dimension

T1mi Tumor ≤1 mm in greatest dimension

T1a Tumor >1 mm but ≤5 mm in greatest dimension

T1b Tumor >5 mm but ≤10 mm in greatest dimension

T1c Tumor >10 mm but ≤20 mm in greatest dimension

T2 Tumor >20 mm but ≤50 mm in greatest dimension

T3 Tumor >50 mm in greatest dimension

T4 Tumor of any size with direct extension to the chest wall and/or to the skin

T4a Extension to the chest wall, not including only pectoralis muscle adherence or invasion

T4b Ulceration and/or ipsilateral satellite nodules and/or edema of the skin

T4c Both T4a and T4b

T4d Inflammatory carcinoma

Regional Lymph Nodes (N)pNX Regional lymph nodes cannot be assessed

pN0 No regional lymph node metastasis

pN0(i−) No regional lymph node metastasis histologically, negative IH C

pN0(i+) Malignant cells in regional lymph node(s) no greater than 0.2 mm

pN0(mol−) No regional lymph node metastasis histologically, negative molecular findings (IHC)

pN0(mol+) Positive molecular findings (RT -PCR), but no metastasis detected by histology or IHC

pN1 Micrometastases; or metastases in one to three axillary nodes; and/or in internal mammary nodes with metastases detected by sentinel lymph node biopsy but not clinically detected

pN1mi Micrometastases (>0.2 mm and/or >200 cells but none >2.0 mm)

pN1a Metastases in one to three axillary nodes; at least one metastasis >2.0 mm

pN1b Metastases in internal mammary nodes with micrometastasis or macrometastases detected by sentinel lymph node biopsy (not clinically detected)

pN1c Metastases in one to three axillary nodes and in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected

pN2 Metastases in four to nine axillary nodes; or in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases

pN2a Metastases in four to nine axillary nodes (at least one tumor deposit >2.0 mm)

pN2b Metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases

pN3 Metastases in ten or more axillary nodes; or in infraclavicular (level III axillary nodes); or in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive level I, II axillary nodes; or in more than three axillary lymph nodes and internal mammary lymph nodes, with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected; or in ipsilateral supraclavicular lymph nodes

Cont’dDistant Metastases (M)

M0 No clinical or radiographic evidence of distant metastases

cM0(i+) No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases

M1 Distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm

Stage Groupings for Breast Cancer

ANATOMIC STA GE PROGNOSTIC GROUP

0 Tis N0 M0

IA T1 N0 M0

IB T0T1

N1miN1mi

M0M0

IIA T0T1T2

N1N1N0

M0M0M0

IIB T2T3

N1N0

M0M0

IIIA T0T1T2T3T3

N2N2N2N1N2

M0M0M0M0M0

IIIB T4 T4 T4

N0 N1 N2

M0M0M0

IIIC Any T N3 M0

IV Any T Any N M1

Therapy• Modalities:• Surgical• Radiotherapy• Chemotherapy• Target Therapy• Endocrine Therapy / Hormonal Therapy

Surgical• Halstedt Radical Mastectomy • Modified Radical Mastectomy (Patey) dissection of

minor pectoral muscle to dissect axillary lymph node until the 3rd level• Modified Radical Mastectomy (Uchincloss and Maaden)

both of pectoral muscles is left intact• Simple Mastectomy (Mc Whirter) plus radiotherapy for

axillary lumph node• BCS (Breast Conserving Surgery) primary tumor

excision with or without axillary lymph node dissection plus radiotherapy

Halsted Radical Mastectomy

The Halsted radical mastectomy involved removing the breast with the overlying skin, the pectoralis major and minor muscles, and the level I, II, and III axillary lymph nodes. (From Bland KI, Copeland EM III. The Breast, 3rd ed. Philadelphia: WB Saunders, 2004.)

The classic Stewart elliptical mastectomy incision. The medial aspect is at the lateral edge of the sternum and the lateral aspect overlies the latissimus dorsi muscle. (From Bland KI, Copeland EM III. The breast, 3rd ed. Philadelphia: WB Saunders, 2004.)

The classic Orr oblique elliptical mastectomy incision. (From Bland KI, Copeland EM III. The breast, 3rd ed. Philadelphia: WB Saunders, 2004.)

Modified Radical Mastectomy

Total mastectomy with and without axillary dissection. A, Skin incisions are generally transverse and surround the central breast and nipple-areolar complex. B, Skin flaps are raised sharply to separate the gland from the overlying skin and then the gland from the underlying muscle. Simple mastectomy divides the breast from the axillary contents and stops at the clavipectoral fascia. C, In modified radical mastectomy, dissection continues into the axilla and generally extends up to the axillary vein, with removal of level I and II nodes. Division of a branch of the axillary vein is shown, with separation of the node-bearing axillary fat from the axillary vein at the superior aspect of the dissection.

Breast Conserving Therapy/Surgery• The aim of local treatment of breast cancer long-term

local disease control with the minimum of local morbidity• Major advantages:

1. An acceptable cosmetic appearance 2. Lower levels of psychological morbidity 3. Equivalence in terms of disease outcome for BCT and

mastectomy

• Indications:• T1, T2 (<4 cm), N0, N1, M0• T2 >4 cm in large breasts• Single clinical and mammographic lesion

Cont’d• Contraindications:

•  T4, N2, or M1 (some localized T4 disease and some patients with limited metastatic disease may be suitable for breast-conserving surgery)

• Patients who prefer mastectomy• Clinically evident multifocal/multicentric disease

• Relative contraindications:• Collagen vascular disease• Large or central tumors in small breasts• Women with a strong family history of breast cancer or BRCA1

and BRCA2 mutation carriers

Breast-conserving surgery. A, Incisions to remove malignant tumors are placed directly over the tumor, without tunneling. A transverse incision in the low axillary region is used for sentinel node biopsy or axillary dissection. The axillary dissection is identical to theprocedure for a modified radical mastectomy. The boundaries of the operation are the axillary vein superiorly, the latissimus dorsi muscle laterally, and the chest wall medially. The inferior dissection enters the tail of Spence (the axillary tail of the breast). Inset, Excision cavity of the lumpectomy. B, In sentinel node biopsy, a similar transverse incision is made, which may be located by percutaneous mapping with the gamma probe if radiolabeled colloid is used. It is extended through the clavipectoral fascia and the true axilla is entered. The sentinel node is located by its staining with dye, radioactivity, or both, and dissected free as a single specimen

Sentinel Lymph Node Biopsy • The aim to avoid complete axillary dissection in

clinically node-negative breast cancer patients• Vital dye and/or radiolabeled colloid is injected into

the parenchyma immediately surrounding a primary breast cancer or in a subareolar manner• Follow the path of lymphatic drainage to sentinel

lymph nodes (SLNs), the first nodes encountered by tumor cells as they metastasize to the axilla

Cont’d

Radiotherapy

•Neoadjuvant radiotherapy before surgery•Adjuvant radiotherapy after surgery•Palliative radiotherapy palliative therapy

Chemotherapy• Standard for chemotherapy agents:

• CMF (Cyclophosphamide – Methotrexate – 5 Fluoro Uracil)• CAF; CEF (Cyclophospamide - Adriamycin/Epirubicin - 5 Fluoro Uracil)• T-A (Taxanes/Paclitaxel/Doxetacel - Adriamycin)• Gapecitabine (Xeloda-oral)• Others, such as Navelbine, Gemcitabine (+cisplatinum)

• Time to administer chemotherapy as:• Neoadjuvant • Adjuvant• Therapeutic for Metastatic Breast Cancer with palliative purpose, without

discourage the chance to extend survival • Palliative to increase the quality of life• Metronomic chemotherapy (cyclophospamide) anti angiogenesis

Chemotherapy Agents and Combinations

Con’t• Dosage and Combination of Chemotherapy agents:• Adjuvant : 6 cycles• Neoadjuvant : 3 cycles• Therapeutic: Until no metastases were found or intoxicity

was developed• Palliative : Long term therapy with palliative purpose

Molecular Targeting Therapy• Indications:• Expression of spesific protein in cancer tissues:

• HER2/Neu : Trastuzumab• VEGF/R : Bevacizumab

• Ussually in combination with chemotherapy• Doxorubicin-Cyclophosphamide followed by paclitaxel or

MDACC trastuzumab combined with palitaxel and FEC

• Dosage:• Loading dose 4 mg/kg, followed by 2 mg/kg every week until

12 weeks• Alternatively, 2 mg/kg given weekly for 40 weeks

Endocrine Therapies• Ovarian suppression/ablation (premenopausal women)• Selective estrogen receptor modulators (tamoxifen,

toremifene)• Dosage: 10 mg/day twice or 20 mg/day once for 5 years

• Aromatase inhibitors (anastrozole, letrozole, exemestane; postmenopausal women)• Antiestrogens (fulvestrant; postmenopausal women)• Progestins (megestrol and medroxyprogesterone)• Other steroid hormones (high-dose estrogens,

androgens; principally of historical interest)

Non Invasive Breast Cancer• Ductal Carcinoma In Situ (DCIS)• Simple Mastectomy• BCT / BCS• Adjuvant therapy

• Patients with high risk of recurrence (age ≤ 35 years old, ER -, PR -, overexpression of HER2, metastases to axillary lymph node

• Radiotherapy, except for tumor with diameter < 1 cm, adequate surgical margin and low grade

• Hormonal therapy ER and/or PR positive without history of thromboembolism

• Lobular Carcinoma In Situ (LCIS)• Tumor excision and good follow up• Adjuvant therapy Tamoxifen

Invasive Breast Cancer• Early Stage• Surgical

• BCS/BCT• Modified Radical Mastectomy• Surgical Reconstruction

• Adjuvant Therapy • Based on lymph node status, age, size of primary tumor,

performance status, HER-2/Neu expression, ER/PR status, nuclear grade

• Pre-menopause, N+, ER/PR + chemotherapy and tamoxifen• Post-menopause, N+, ER/PR + tamoxifen/Aromatase inhibitor

with/without chemotherapy• Pre-menopause, N-, ER/PR - consider other prognostic factor

Common Reconstructive Options after Mastectomy

Type Advantages Disadvantages

Implant One stage procedure, minimal prolongation, hospitalization, or recovery.Low cost.

Poor symmetry if skin removed or in large ptotic breasts.Capsular contracture, leakage, rupture possible.

Tissue expander Short operative time.Hospitalization, recovery not prolonged.Low cost.

Multiple physician visits postop. Poor symmetry large or ptotic breasts.Capsular contracture, leakage rupture possible.

Latissimus dorsi flap Very low risk of flap loss.Natural contour with autogenous tissue.

Donor site scar.Usually requires an implant.Moderate prolongation hospitalization and recovery.

Cont’dType Advantages Disadvantages

Transverse rectus abdominous myocutaneous (TRAM) flap

Natural contour. Good match for large or ptotic breasts.Abdominoplasty.

Donor site scar.Fat necrosis, flap loss possible.Abdominal wall weakness plus hernia.Significant prolongation hospitalization plus recovery.

Deep inferior epigastric perforator (DIEP) flap

Natural contour.Muscle sparing.Abdominoplasty.

Donor site scar.Need for microsurgeon.Flap loss possible.Moderate prolongation hospitalization plus recovery.

Superior gluteal artery perforator flap

Natural contour.Alternative donor site.

Donor site scar.Need for microsurgeon.Flap loss possible.Moderate prolongation hospitalization plus recovery.

Patients are marked preoperatively in the standing position for anatomic landmarks as well as the proposed DIEP flap procedure. Slight adjustments to the suprapubic marking can be made during surgery to assure a tension-free closure of the abdomen

Isolation of the DIEP flap on the selected perforators proceeds under loupe magnification, and begins by opening the anterior rectus sheath around each perforator. A very small cuff of the fascia can be harvested along with each perforator, as shown here, but routinely, no fascia is harvested.

The rectus abdominis muscle is split along the direction of its fibers during DIEP flap harvest. All small side branches originating from the selected perforators or the deep inferior epigastric vessels are carefully ligated and divided as the dissection proceeds.

End-to-end microanastomoses are fashioned between the deep inferior epigastric vessels and either the thoracodorsal or internal mammary recipient vessels. Once perfusion is re-established, the DIEP flap is debulked, contoured, and inset. Areas of the skin island underlying the native mastectomy flaps are deepithelialized in situ.

Invasive Breast Cancer• Locally Advanced Breast Ca• Surgical

• Modified Radical Mastectomy• Halstedt Radical Mastectomy

• Neoadjuvant Therapy• Chemotherapy AC, CAF/CEF, T-A• Hormonal therapy only given when ER/PR + and the drug is Aromatase

inhibitor (Ais)

• Inflammatory Breast Ca• Sandwich therapy

• Neoadjuvant chemotherapy• Surgery or Radiotherapy• Adjuvant chemotherapy

Cont’d• Metatstatic Breast Cancer• Surgery is not an option• Systemic therapy, such as chemotherapy or hormonal

therapi is therapy of choice• Therapeutic chemotherapy is main option for:

• Visceral metastasis (life threatening metastasis)• Aggressive breast cancer (high grades, HER2 overexpression, ER/PR

-, P53 overexpression)• Young age

• Hormonal therapy ER/PR - , bone metastasis, low grades• Surgery palliative therapy

Pre-operative

•Preparation prior to surgery:• Laboratory examination• Imaging • Respiratory function test• Chest physiotherapy for elderly

Post-operative• Day 1-2:

• Joint movement exercise around surgical site (shoulder and elbow joint gradually isometric)

• Relaxation of neck and chest muscles exercise• Active mobilization• Patient is discharged with the drain if home care is possible

• Day 3-5:• Shoulder and arm movement ipsilateral of surgical site more freely• Relaxation exercise• Free movement• Education to mantain ROM of joints with regular exercise• Education to keep the arm ipsilateral of surgical site healthy

Breast Cancer during Pregnancy• Diagnosis, stadium and therapy are the same with or

without pregnancy• Special consideration CT Scan or Bone Scanning • Therapy:• Surgical (trimester I or II)

• Radical Mastectomy• Modified Radical Mastectomy

• Adjuvant therapy must be postponed until trimester II and III• Radiotherapy after delivery• Chemotherapy trimester III, after surgery

Phylloides Tumor (malignant)• 0,5% - 1% breast cancer• Age: 35 – 55 years• Ussually big in size (> 4 cm)• Malignant or not depends on:• Histopatholgy/histotype• Margin• Stromal development• Size

• Surgical complete excision of tumor ~ simple mastectomy

Follow Up

Cont’d

Prognostic Factors • Tumor biology (grade, estrogen receptor status, HER-2 status)• Performance status• Cancer related symptoms• Sites of recurrence• Number of sites of recurrence• Prior adjuvant therapy• Disease-free interval• Prior therapy for metastatic disease• Response/duration of treatment with prior therapy for

metastatic disease

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