The Power of Pink: Diagnosis & Treatment of Breast Disease

Tony L. Weaver, D.O.

ObjectivesReview Anatomy & Physiology

Discuss:

● Diagnosis ● Management ● Treatment of benign &

Malignant Breast Disease

It is about YOU!

ANATOMY AND PHYSIOLOGYBreast development

• Breast formed from ectoderm milk streak

• Estrogen – duct development (double layer of columnar cells)

• Progesterone – Lobular development• Prolactin – synergizes estrogen and

progesterone

Hormones and Cyclic changes

Estrogen – ↑ breast swelling, growth of glandular tissue

Progesterone – ↑ maturation of glandular tissue; withdrawal causes menses

FSH, LH surge – cause ovum release

After menopause, lack of estrogen and progesterone results in atrophy of breast tissue

Lymphatic drainage

• 97% is to the axillary nodes• 2% is to the internal mammary nodes

• Any quadrant can drain to the internal mammary nodes

• Supraclavicular nodes –considered N3 disease

• Primary axillary adenopathy – #1 is lymphoma

You’ve Got a lot of Nerve

Medial pectoral nerve → pectoralis major and

pectoralis minor

Lateral pectoral nerve ---> Pectoralis Major

only

Intercostobrachial Nerve – lateral cutaneous

branch of the 2nd intercostal nerve

Nerve

Name that Nerve

Important NervesLong thoracic nerve – innervates serratus anterior; injury results in winged scapula

Thoracodorsal Nerve –

innervates latissimus dorsi; injury results in weak arm pull-ups and adduction

Vessels● Internal thoracic artery

● Intercostal arteries,

● Thoracoacromial artery

● lateral thoracic artery

Batson’s plexus –

● valveless vein plexus

● direct hematogenous metastasis to spine

Lateral thoracic artery supplies serratus anterior

Thoracodorsal artery supplies latissimus dorsi

BREAST CANCER

● Breast CA decreased in economically poor areas

● Japan has lowest rate of breast CA worldwide

● U.S. breast CA risk – 1 in 8 women (12%); 5% in women with

no risk factors

● Screening decreases mortality by 25%

● Untreated breast cancer – median survival 2–3 years

● 10% of breast CAs have negative mammogram and negative

ultrasound

● Clinical features of breast CA – distortion of normal

architecture; skin/nipple distortion or retraction; hard,

tethered, indistinct borders

Breast Cancer Risk

Greatly increased risk (relative risk > 4)• BRCA gene in patient with family history of breast CA

• ≥ 2 primary relatives with bilateral or premenopausal breast CA• DCIS (ipsilateral breast at risk) and LCIS (both breasts have same high risk)• Fibrocystic disease with atypical hyperplasia

Moderately increased risk (relative risk 2–4) – prior breast cancer, radiation exposure, first-degree relative with breast cancer, age > 35 first birth

Lower increased risk (relative risk < 2) – early menarche, late menopause,

nulliparity, proliferative benign disease, obesity, alcohol use, hormone replacement therapy

What’s a Mammogram?

Screening

• Mammogram every 2–3 years after age 40, then yearly after 50

• High-risk screening – mammogram 10 years before the youngest age of

diagnosis of breast CA in first-degree relative

• No mammography in patients < 40 unless high risk → hard to interpret

because of dense parenchyma

• Want to decrease radiation dose in young patients

Mammography

• Has 90% sensitivity/specificity• Sensitivity increases with age as the dense parenchymal tissue is replaced with fat• Mass needs to be ≥ 5 mm to be detected• Suggestive of CA – irregular borders; spiculated; multiple clustered, small,

thin, linear, crushed-like and/or branching calcifications; ductal asymmetry, distortion of architecture

What is BIRADS?

Nice → NegativeBreast → BenignPlease → Probably BenignShow → Suspicious for Malignancy Me → Highly Suspicious for Malignant

BiRADS

Risk Assessment ToolsGail Model

● Age, menarche, age of first live birth, previous history of biopsies (benign or atypia), family history of 1st degree

relatives

● Calculates risk at 5 years and to age 90 of developing breast cancer

Gail Pitfalls

● Underestimates family history (accounts for only disease in first

degree relatives), no paternal FH

● Heavily weighted on biopsy history

● Not incorporate age at diagnosis● Not accepted estimate for need for MRI

Other alternatives: Claus tables, BRCAPRO

and BOADICEA (genetic counselor) more in

depth family assessment

● Average woman risk of BRCA 1 or 2 mutation: 1/450 to 1/800● Women of Ashkenazi descent risk of BRCA mutation: 1/40● 10% of women with breast cancer have a BRCA mutation

BRCA 1● Younger age at cancer presentation

30-45yo

● Premenopausal● Lifetime risk for breast cancer 50-

80%● Risk of contralateral breast cancer

60%● Breast cancers tend to be triple

negative

● Ovarian cancer risk 40-60%

BRCA2● Same age for development of breast cancer

as general population

● Lifetime risk of BC same as BRCA1● Risk for contralateral BC is same as

BRCA1● Breast cancers tend to be ER+

● Ovarian cancer risk 16-30%● Male breast cancer risk 6%● Increased risk for prostate, pancreas,

melanoma

Ductal Cancer85% of all breast CA

Medullary – smooth borders, ↑ lymphocytes, bizarre cells, more favorable prognosis

Tubular – small tubule formations, more favorable prognosis

Mucinous (colloid) – produces an abundance of mucin, more favorable prognosis

Scirrhotic – worse prognosis

Tx: MRM or BCT with postop XRT

Good● Tubular● Papillary● Mucinous● Adenoid cystic

Bad● Medullary● squamous

Prognostics of Invasive Breast Cancer

Considered T4 disease

● Very aggressive → median survival of 36 months

● Has dermal lymphatic invasion, which causes peau d’orange lymphedemaappearance on breast; erythematous and warm

Tx: Neoadjuvant chemo, then MRM, then adjuvant chemo-XRT

Inflammatory Cancer

Occult breast CA – breast CA that

presents as axillary metastases with

unknown primary; Tx: MRM (70% are found to have breast CA)

Almost all women with recurrence die of diseaseIncreased recurrences and metastases occur with positive nodes, large tumors,

negative receptors, unfavorable subtype

Metastatic flare – pain, swelling, erythema

in metastatic areas; XRT can help• XRT is good for bone metastases

What is the most important prognostic staging

factor??

Nodes

• 0 nodes positive 75% 5-year survival

• 1–3 nodes positive 60% 5-year survival

• 4–10 nodes positive 40% 5-year survival

Survival is directly related to the number of positive nodes

What is the MOST COMMON Site of Distal Mets?

Bone – most common site for distant metastasis (can also go to lung, liver, brain)

Takes approximately 5–7 years to go from single malignant cell to 1-cm tumor

Central and subareolar tumors have increased risk of multicentricity

Invasive BC treatment (all types)● Excise to negative margins (no

tumor at ink, most aim for >2mm margin)

● XRT if had successful BCT● SLNB +/-ALND in all cases

Chemotherapy

● Hormonal (antiestrogen)● Chemotherapy● Monoclonal antibody

(trastuzumab/Herceptin)

ALND – take level I and II nodes

Complications of MRM– infection, flap necrosis, seromas

Complications of ALND• Infection, lymphedema, lymphangiosarcoma• Axillary vein thrombosis – sudden, early, postop

swelling• Lymphatic fibrosis – slow swelling over 18 months• Intercostal brachiocutaneous nerve injury –

hyperesthesia of inner arm and lateral chest wall; most commonly injured nerve after mastectomy; no significant sequelae

• Drains – leave in until drainage < 40 cc/day

Breast Surgery Basics

ReceptorsPositive receptors:

● better response to hormones, chemotherapy, surgery, and better overall prognosis● Receptor-positive tumors are more common in postmenopausal women

Progesterone receptor–positive tumors have better prognosis than estrogen receptor–positive tumors

Tumors that are both progesterone receptor &estrogen receptor positive have the best prognosis 10% of breast CA is negative for both receptors

During SLNB – if no radiotracer or dye is found…??

• Fewer complications than ALND

• Only for malignant tumors > 1 cm

• Patients with clinically positive nodes; Need ALND

• Accuracy best when primary tumor is present

(finds the right lymphatic channels)

• Lymphazurin blue dye or radiotracer is injected

directly into tumor area Risk: Type I hypersensitivity reactions

• Usually find 1–3 nodes; 95% of the time, the

sentinel node is found

Contraindications – pregnancy, multicentric disease,

neoadjuvant therapy, clinically positive nodes, prior

axillary surgery, inflammatory or locally advanced

disease

SLNB

10% of all breast CAs

Does not form calcifications; extensively infiltrative; ↑ bilateral, multifocal, and multicentric disease

Signet ring cells confer worse prognosis

Tx: MRM or BCT with postop XRT

Lobular Cancer

Male Breast Cancer

• < 1% of all breast CAs; usually ductal• Poorer prognosis because of late presentation

• Have ↑ pectoral muscle involvement

• Associated with steroid use, previous XRT, family history, Klinefelter’s

syndrome

• Tx: modified radical mastectomy (MRM)

Breast Cancer Treatment

What is a Name????

Surgical Options● Lumpectomy/Partial

Mastectomy/BCT● Mastectomy

Survival is equivalent

● Rates of local recurrence are higher with BCT than with Mastectomy.

Compared BCT vs Mastectomy Alone vs Mastectomy w/ Radiation

Large Retrospective Study 132,149 pts

Breast conservation therapy 70% , Mastectomy alone 27% of patients, Mastectomy with radiation 3% of

patients.

5-year breast cancer–specific survival rates 97%, 94%, and 90% (P < .001)

10-year breast cancer–specific survival rates were 94%, 90%, and 83% (P < .001).

Multivariate analysis showed that women undergoing BCT had a higher survival rate than those undergoing mastectomy alone (hazard ratio, 1.31; P < .001) or mastectomy with radiation (hazard ratio, 1.47; P < .001).

BCT

Lumpectomy

Quadrectomy+ ALND or SLNBcombined

with

Postop XRT; need 1-cm

margin

Breast-Conserving therapy

BCT with XRT

• Need to have negative margins (1 cm) following BCT before starting XRT

• 10% chance of local recurrence, usually within 2 years of 1st operation, need to re-stage with recurrence

• Need salvage MRM for local recurrence

Radical Mastectomy

Radical Mastectomy

Modified Radical Mastectomy

Modified Radical

Modified radical mastectomy

• Removes all breast tissue, including the nipple areolar complex

• Includes axillary node dissection level I nodes

Simple Mastectomy

Simple Mastectomy

A simple mastectomy (left) removes the breast tissue, nipple, areola and skin but not all the lymph nodes

Subcutaneous Mastectomy

Subcutaneous Mastectomy

Chemotherapy• TAC (taxanes, Adriamycin, and cyclophosphamide) for 6–12 weeks• Positive nodes – everyone gets chemo except postmenopausal women with positive estrogen receptors → they can

get hormonal therapy only witharomatase inhibitor (anastrozole)• > 1 cm and negative nodes – everyone gets chemoexcept patients with positive estrogen receptors → they can get

hormonal therapy only with tamoxifen if they are premenopausal or aromatase inhibitor (anastrozole) if they are

postmenopausal• < 1 cm and negative nodes – no chemo; hormonal therapy as above if positive estrogen receptors

• After chemo, patients positive for estrogen receptorsshould receive appropriate hormonal therapy• Both chemotherapy and hormonal therapy have been shown to decrease recurrence and improve survival

Taxanes – docetaxel, paclitaxel

Tamoxifen – decreases risk of breast CA by 50%

• 1% risk of blood clots; 0.1% risk of endometrial CA

● 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy.

● 5 year Invasive disease–free survival was 93.8%● Rate of freedom from recurrence of breast cancer at a distant site was 99.3%● The rate of freedom from recurrence of breast cancer at a distant or local–regional site was

98.7% Rate of overall survival was 98.0% (95% CI, 97.1 to 98.6).

Pts with hormone-receptor–positive, HER2-negative, axillary node–negative breast cancer with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone.

Radiotherapy• Usually consists of 5,000 rad for BCT and XRT

• Complications of XRT – edema, erythema, rib fractures, pneumonitis, ulceration, sarcoma, contralateral breast CA

• Contraindications to XRT – scleroderma (results in severe fibrosis and necrosis), previous XRT and would exceed recommended dose, SLE (relative), active rheumatoid arthritis

(relative)

Indications for XRT after mastectomy:• > 4 nodes

• Skin or chest wall involvement• Positive margins• Tumor > 5 cm (T3)

• Extracapsular nodal invasion• Inflammatory CA• Fixed axillary nodes (N2) or internal mammary nodes (N3)

Which one of the following represents a contraindication to breast conservation therapy?

A. Previous breast irradiationB. Tumors larger than 3 cm diameterC. Unifocal diseaseD. Ductal carcinoma in situE. Tumors in large fatty breasts

In a female patient with a primary T2N0M0 breast cancer, which one of the following is correct?

A. Her overall survival is unaffected whether breast conservation surgery or mastectomy is performed.

B. Her risk of local recurrence is unaffected by whether breast conservation surgery or mastectomy is performed.

C. Postoperative radiotherapy is required irrespective of whether breast conservation surgery or mastectomy is performed.

D. She has a 95% chance of being alive at five years given her disease stage.

E. Sentinel lymph node biopsy for this patient has only 65% sensitivity and specificity for breast cancer.

• Tends to present late, leading to worse prognosis

• Mammography and ultrasound do not work as well during

pregnancy

• Try to use ultrasound to avoid radiation• If cyst, drain it and send FNA for cytology

• If solid, perform core needle biopsy or FNA

• If core needle and FNA equivocal, need to go to excisional

biopsy

If breast CA

• 1st trimester – MRM

• 2nd trimester – MRM

• 3rd trimester – MRM or if late can perform lumpectomy with

ALND and postpartum XRT• No XRT while pregnant; no breastfeeding after delivery

Pregnancy & Breast Cancer

Cystosarcoma Phyllodes• 10% malignant, based on mitoses per

high-power field (> 5–10)• No nodal metastases, hematogenous

spread if any (rare)

• Resembles giant fibroadenoma; has

stromal and epithelial elements

(mesenchymal tissue)• Can often be large tumors

Tx: WLE with negative margins; no ALND

Paget’s Disease• Scaly skin lesion on nipple; biopsy

shows Paget’s cells

• Patients have DCIS or ductal CA in breast

Tx: need MRM if cancer present;

otherwise simple mastectomy (need to

include the nipple-areolar complex with Paget’s)

Stewart–Treves Syndrome• Lymphangiosarcoma from chronic lymphedema following axillary dissection• Patients present with dark purple nodule or lesion on arm 5–10 years after surgery

● Most nipple discharge is benign● All need a history, breast exam, and

bilateral mammogram● Try to find the trigger point or mass

on exam

Nipple Discharge

Nipple Discharge

Green discharge – usually due to fibrocystic disease

• Tx: if cyclical and nonspontaneous, reassure patientBloody discharge – most commonly intraductal papilloma; occasionally ductal CA• Tx: need ductogram and excision of that ductal areaSerous discharge – worrisome for cancer, especially if coming from only 1 duct or spontaneous

• Tx: excisional biopsy of that ductal areaSpontaneous discharge – no matter what the color or consistency is, this is worrisome for CA → all

these patients need excisional biopsy of duct area causing the discharge

Nonspontaneous discharge (occurs only with pressure, tight garments, exercise, etc.)– not as worrisome but may still need excisional biopsy (eg if bloody)

May have to do a complete subareolar resection if the area above cannot be properly identified (no trigger point or mass felt)

Periductal Mastitis

(mammary duct ectasia or plasma cellmastitis)

Symptoms: noncyclical mastodynia, erythema, nipple retraction, creamy discharge from nipple; can have sterile or infected subareolar abscess

• Risk factors – smoking, nipple piercings• Biopsy – dilated mammary ducts, inspissated secretions, marked periductal

inflammation

Tx: if typical creamy discharge is present that is not bloody and not associated with nipple retraction, give antibiotics and reassure; if not or if it recurs, need to rule out inflammatory CA (incisional biopsy including the skin)

Mastodynia– pain in breast; rarely represents breast CADx: H & P, MMG

Cyclic mastodynia – pain before menstrual period; most commonly from fibrocystic diseaseContinuous mastodynia – continuous pain, most commonly represents acute or subacute infection;

continuous mastodynia is more refractory to treatment than cyclic mastodynia enlarge, need

excisional biopsyIn patients > 40 years old → excisional biopsy to ensure diagnosis

Tx: Danazol, OCPs, NSAIDs, evening primrose oil, bromocriptine

Discontinue caffeine, nicotine, methylxanthines

Poland’s Syndrome

1. Hypoplasia of chest wall & Shoulder,

2. Amastia3. no pectoralis

muscle

– most commonly associated with breastfeeding

S. aureus most common.● nonlactating women think chronic

inflammatory diseases (eg actinomyces) or autoimmune disease (eg SLE)

● may need to rule out necrotic cancer (need incisional biopsy including the skin)

Infectious Mastitis

Galactorrhea● Is often associated with amenorrhea

● can be caused by ↑ prolactin (pituitary

prolactinoma)

Meds: OCPs, TCAs, phenothiazines, Reglan,

alpha-methyl dopa, reserpine

Look for source:

Prolactin level, Thyroid work up, MRI, medications

Gynecomastia● 2-cm pinch; MCC idiopathic● Assoc. w cimetidine, spironolactone,

marijuana

Tx: Many regress; may need to resect if

cosmetically deforming or causing social problems

Intraductal papillomaMCC bloody nipple discharge

usually small, nonpalpable, & close to the nippleNOT premalignantcontrast ductogram to find papilloma, then needle localization

Tx: subareolar resection of the involved duct and papilloma

Mondor’s Disease– superficial vein thrombophlebitis of

breast; feels cordlike, can be painful• Associated with trauma and

strenuous exercise

• Usually occurs in lower outer

quadrant

• Tx: NSAIDs

Fibrocystic Disease• Lots of types: papillomatosis, sclerosing adenosis,

apocrine metaplasia, duct adenosis, epithelial hyperplasia, ductal hyperplasia, and lobular hyperplasia

• Symptoms: breast pain, nipple discharge (usually yellow to brown), lumpy breast tissue that varies with hormonal cycle

Only cancer risk is atypical ductal or lobular hyperplasia – need to resect these lesions

Do not need to get negative margins with atypical hyperplasia; just remove all suspicious areas (ie calcifications) that appear on mammogram

Fibroadenoma• Most common breast lesion in adolescents and young women; 10% multiple

• Usually painless, slow growing, well circumscribed, firm, and rubbery• Often grows to several cm in size and then stops

• Can change in size with menstrual cycle and can enlarge in pregnancy

• Giant fibromas can be > 5 cm (treatment is the same)• Can have large, coarse calcifications (popcorn lesions) on mammography from

degeneration

In patients < 40 years old:1) Mass needs to feel clinically benign (firm, rubbery, rolls, not fixed)

2) Ultrasound or mammogram needs to be consistent with fibroadenoma3) Need FNA or core needle biopsy to show fibroadenoma

• Need all 3 of the above to be able to observe, otherwise need excisional biopsy