breast patho

4. Nipple Discharge
 If the history describes bilateral nipple
discharge, think of prolactinoma.
 Order prolactin levels and TSH levels.
• Nonbloody nipple
discharge = most likely
intraductal papilloma.
May also be malignancy.
• Bloody nipple
discharge = most likely
malignancy

5. Most Common Cause
 The most common cause of unilateral
nonbloody nipple discharge is
intraductal papilloma.
 It commonly presents with watery,
serous or serosanguinous fluid
discharge.
 The likelihood of cancer is greater if
there is an associated palpable mass,
involvement of more than one duct or
bloody discharge.

6. Diagnostic Testing
 Mammogram: Look for underlying
masses or calcifications.
 Surgical duct excision: Perform this for
definitive diagnosis.
 Cytology is not helpful in the diagnosis
and is never the answer for nipple
discharge.

7. Breast Mass-Fibrocystic
Disease
 This classically presents in a woman age 20–
50 with cyclical, bilateral painful breast lump(s).
 A clue to the diagnosis is that the pain will vary
with the menstrual cycle.
 A simple cyst will have sharp margins and
posterior acoustic enhancement on ultrasound.
It will collapse on fine-needle aspiration FNA.
 Treatment is oral contraceptive
pills/medications (OCP).
 In patients with severe pain, danazol may be
used.

8. Mammogram

10. Answer : C

11. Fibroadenoma
 This classically presents as a discrete,
firm, nontender, and highly mobile
breast nodule.
 A clue to the diagnosis is a mass that’s
highly mobile on clinical exam.
 Fibroadenomas are made up of stromal
and epithelial cells.

13. Diagnostic Testing
 The steps in diagnosis of any patient
(including pregnant women) with a
breast mass are as follows:
 1. Clinical breast examination (CBE)
 2. Imaging: Ultrasound or diagnostic
mammography (if patient > 40)
 3. Fine-needle aspiration (FNA) biopsy

14. Treatment
 No treatment is necessary. Surgical
removal can be done if the mass is
growing
Never diagnose a simple
cyst on clinical exam
alone. The diagnosis must
be confirmed with either
ultrasound or FNA.

16. A 30-year-old woman complains of bilateral
breast enlargement and tenderness,
which fluctuates with her menstrual cycle. On
physical examination, the breast
feels lumpy, and there is a painful, discrete 1.5-
cm nodule. A fine-needle aspiration
is performed, and clear liquid is withdrawn. The
cyst collapses with aspiration.
Which of the following is the next step in
management?
a. Clinical breast exam in 6 weeks
b. Core needle biopsy
c. Mammography
d. Repeat FNA in 6 weeks
e. Ultrasound in 6 weeks

17.  Answer: A. Clinical breast exam in 6
weeks is appropriate follow-up for a
cystic mass that disappears after FNA. If
the mass recurs on the 6-week follow-
up, FNA may be repeated, and a core
biopsy can be performed.

18. When do you answer the
following?
1. Ultrasound:
 First step in workup of a palpable mass
that feels cystic on exam.
 Imaging test for younger women with
dense breast

19. Normal breast US

21. 2. Mammography
Mammography (> 50 years old) and biopsy (or
biopsy alone if < 40 years old):
 Cyst recurs > twice within 4 to 6 weeks.
 There is bloody fluid on aspiration.
 Mass does not disappear completely upon
FNA.
 There is bloody nipple discharge (excisional
biopsy).
 There are skin edema and erythema suggestive
of inflammatory breast carcinoma (excisional
biopsy).

22. Mammography
Mammogram should be
done before biopsy. Biopsy
distorts radiography.

23. 3. Fine-needle aspiration or core biopsy
is needed for a palpable mass. May be done
after ultrasound or instead of ultrasound.
4. Cytology:
 Any aspirate that is grossly bloody must be
sent for cytology.
 Observation with repeat exam in 6–8 weeks:
-- Cyst disappears on aspiration, and the fluid is
clear.
-- Needle biopsy and imaging studies are
negative.
Core biopsy is superior to
FNA.

24. A 47-year-old woman completes her yearly
mammogram and is told to return for
evaluation. The mammogram reveals a “cluster”
of microcalcifications in the left
breast. What is the most appropriate next step
in management?
a. Excision biopsy
b. Core needle biopsy
c. Repeat screening mammogram in 6 months
d. Repeat screening mammogram in 12 months
e. Ultrasound

25. Answer: B. A cluster of microcalcifications
are mostly benign; however, approximately
15–20 percent represent early cancer. The
next step in workup is core needle biopsy
under mammographic guidance.

26. Breast Cancer- Preinvasive
Diseases
 Both ductal carcinoma in situ (DCIS) and lobular
carcinoma in situ (LCIS) increase the risk of
invasive disease. If biopsy reveals
 DCIS, then schedule surgical resection with clear
margins (lumpectomy; i.e., breast conserving
surgical resection) and give radiation therapy (RT)
and tamoxifen for 5 years to prevent the
development of invasive disease.
 LCIS, then tamoxifen alone given for 5 years to
reduce risk of development of breast cancer. It is not
necessary to perform surgery.
 Note that LCIS is classically seen in premenopausal
women.

27.  Tamoxifen is an estrogen receptor
antagonist in the breast tissue. It acts as
an endometrial agonist.
 Agonist drugs bind to and activate a
receptor. Agonists cause an action.
 Antagonists are drugs with high affinity
(bind to receptors well) but no efficacy
(do not make the receptors work).
Antagonists block an action.

28. schedule surgical resection with clear margins (lumpectomy; i.e., breast
conserving surgical resection) and give radiation therapy (RT) and
tamoxifen for 5 years to prevent the development of invasive disease

29. tamoxifen alone given for 5 years to reduce risk of
development of breast cancer. It is not necessary to perform
surgery

30. Risks associated with tamoxifen use:
• Endometrial carcinoma
• Thromboembolism
Contraindications:
• Patient is active smoker
• Previous thromboembolism
• High risk for thromboembolism

31. Invasive Breast Diseases
1. Invasive ductal carcinoma is the most
common form of breast cancer (85 percent
of all cases). It is unilateral. It metastasizes
to bone, liver, and brain.
2. Invasive lobular carcinoma accounts for
10 percent of breast carcinomas. It tends to
be multifocal (within the same breast) and
is bilateral in 20 percent of cases.

32. 3. Inflammatory breast cancer is
uncommon, grows rapidly, and metastasizes
early. Look for a red, swollen, and warm
breast and pitted, edematous skin (classic
peau d’orange appearance).
4. Paget’s disease of the breast/nipple
presents with a pruritic, erythematous, scaly
nipple lesion. It’s often confused with
dermatosis-like eczema or psoriasis. Look
for an inverted nipple or discharge.

35. Established risk factors for breast
cancer:
 Age ≥ 50 years old
 Familial BRCA1/BRCA2 mutation carrier
 Exposure to ionizing radiation
 First childbirth after age 30 or nulliparity
 History of breast cancer
 History of breast cancer in a first-degree
relative
 Hormone therapy
 Obesity (BMI ≥ 30 kg per m2)

36. When are BRCA1 and BRCA2
gene testing indicated?
 Family history of early-onset (< 50
years of age) breast cancer or ovarian
cancer
 Breast and/or ovarian cancer in the
same patient
 Family history of male breast cancer
 Ashkenazi Jewish heritage

37. Treatment
 Primary treatment of invasive carcinoma when
tumor size < 5 cm is lumpectomy + radiotherapy
± adjuvant therapy ± chemotherapy.
 Sentinel node biopsy is preferred over axillary
node dissection.
 Always test for estrogen and progesterone
receptors and HER2/neu receptor protein.
 Primary treatment of inflammatory, tumor size >
5 cm, and metastatic disease is systemic
therapy.

38. Breast cancer screening guidelines per the U.S.-
Preventive Services Task Force (USPSTF):
• Mammogram every 1–2 years recommended for ages
50–74.
• Screening before age 50 is no longer routinely
recommended.
• Women < 50 should only consider mammographic
screening based on high individual risk for early onset
breast cancer.
• Teaching breast-self exam is no longer encouraged.
• Clinical breast exams are no longer routinely advised.

39. A 68-year-old woman visits her primary care
physician with a solid peanut-shaped
hard mass in the upper outer quadrant of the left
breast. A biopsy of the lesion
reveals “infiltrating ductal breast cancer.” What is
the next step in management?
a. Lumpectomy plus radiotherapy
b. Modified radical mastectomy
c. Modified radical mastectomy plus radiotherapy
d. Neoadjuvant chemotherapy plus lumpectomy
plus radiotherapy
e. Tamoxifen and radiotherapy

40. Answer: A. Breast-conserving surgical
therapy (lumpectomy) plus radiotherapy is
the standard of care for invasive disease.
There is no survival benefit with modified
radical mastectomy.

41. When is breast-conserving
therapy not the answer?
 Pregnancy
 Prior irradiation to the breast
 Diffuse malignancy or ≥ 2 sites Is
separate quadrants
 Positive tumor margins
 Tumor > 5 cm

42. When is adjuvant hormonal therapy
included in management?
 In any hormone receptor-positive (HR+) tumors,
regardless of age and regardless of menopausal
status, stage, or type of tumor
 There is the greatest benefit when both ER+ and
PR+ receptors are present.
 Therapy is nearly as good when there are only
ER+ estrogen receptors.
 Adjuvant hormonal therapy has the least benefit
when only PR+ receptors are present.

43.  Tamoxifen competitively binds estrogen
receptors.
-- Five-year treatment → 50 percent decrease in the
recurrence, 25 percent decrease in mortality.
-- May be used in pre- or postmenopausal patients.
 Aromatase inhibitors (anastrozole, exemestane,
letrozole) block peripheral production of estrogen.
-- This is the standard of care in HR+
postmenopausal women (more effective than
tamoxifen).
-- Does not cause menopausal symptoms but does
increase the risk of osteoporosis.

44.  LHRH analogs (e.g., goserelin) or ovarian
ablation (surgical oophorectomy or external
beam RT) is an alternative or an addition to
tamoxifen in premenopausal women.

45. Benefits of Tamoxifen
• ↓ incidence of contralateral breast
cancer
• ↑ bone density in postmenopausal
women
• ↓ fractures
• ↓ serum cholesterol
• ↓ cardiovascular mortality risk

46. Adverse Effects of
Tamoxifen
 • Exacerbates menopausal symptoms
 • ↑↑ risk of endometrial cancer (1% in
postmenopausal women after 5 yrs
therapy)
 • ↑↑ risk of thromboembolism
TIP: All women with a history of tamoxifen
use and vaginal bleeding need evaluation
& endometrial biopsy.

47. When is chemotherapy
included in management?
 Tumor size > 1 cm
 Lymph node-positive disease

48. When is trastuzumab included in
management?
 It is indicated for metastatic breast
cancer overexpressing HER2/neu.
 Trastuzumab is a monoclonal antibody
directed against the extracellular domain
of the HER2/neu receptor and is used to
treat and control visceral metastatic
sites.

49. If the case describes invasive
breast cancer in an
 HR-negative, pre- or postmenopausal
womanGive chemotherapy ± RT alone.
 HR-positive, premenopausal woman
 Give chemotherapy ± RT + tamoxifen.
 HR-positive, postmenopausal woman
 Give chemotherapy ± RT + aromatase
inhibitor