MANAGEMENT OF THE BREAST LUMP AND PMS
| WORK-UP OF THE BREAST LUMP —Armando Giuliano, MD, Clinical Professor of Surgery, David Geffen School of
Medicine at the University of California, Los Angeles, and Chief of Surgical Oncology, John Wayne Cancer Institute, Santa
Monica, California
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| Risk factors: ≤85% risk for breast cancer with BRCA-1 and BRCA-2 genetic mutations; positive family history; personal
history of breast cancer; proliferative breast disease; hormone replacement therapy (HRT); consider age at menarche,
menopause, and first live birth
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| Evaluation: patient history; ask how long patient has had mass, whether mass fluctuates with menses, and whether mass painful
or tender; clinical signs and symptoms—discrete lump accounts for ≈75% of cases; vague swelling; discomfort; nipple retraction;
discharge (eg, bleeding); skin changes or metastases without obvious primary; findings on mammography—
discrete abnormality that may or may not be palpable most common finding of breast cancer; breast cancers can occur as high
as clavicle, as low as costal margin to sternal border, and laterally to latissimus; physical examination—look for symmetry;
ask patient to lift arms up over shoulder and squeeze hips; check lymph nodes; have patient move pectoral muscles; look for
skin changes, retraction of nipple, dimpling, and edema; begin palpation; examine breasts while patient seated and while lying
down; breast parenchyma of postmenopausal women usually soft or mildly nodular; diffuse nodularity (lumpiness; “like a
cluster of grapes in a plastic bag”) often felt in premenopausal women or postmenopausal women on HRT; patients may have
areas of increased nodularity in upper outer quadrants or subareolar tissue; usually symmetric; look for something that feels
different; normal structures (eg, fat lobule, rib) often feel like masses
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| Breast masses: nonneoplastic—most common; fibrocystic disease; galactoceles; stromal fibrosis; inflammatory masses
(eg, mastitis); fat necrosis clinically indistinguishable from cancer; hematoma after trauma; granuloma; Mondor’s disease;
sebaceous cyst; neoplastic—can be benign (eg, fibroadenoma, papilloma), intermediate (eg, cystosarcoma phyllodes), or
malignant (eg, carcinoma, cystosarcoma); peau d'orange—resembles orange peel; invasion of dermal lymphatics causes
edema of breasts; sign of advanced cancer; seen in women who underwent lumpectomy and irradiation; Paget’s
disease—presents as small area on nipple; treated for months with topical creams, ointments, and steroids; causes erosion
of nipple; sign of underlying malignancy; inflammatory carcinoma—perform biopsy; freely movable masses can
be malignant
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| Breast imaging: ultrasonography (US) useful for determining whether mass cystic or solid; pneumocystography not recommended;
computed tomography (CT) should be used rarely for breast; magnetic resonance imaging (MRI) frequently
misused; mammography indicated for screening and for evaluating mass or change in breast; look for occult lesions; start
mammography at earlier age in women at increased risk
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| Mammographic findings: benign—mass lesions round with smooth margins; fibrous tissue intact; coarse calcifications;
symmetric; lesions do not grow; malignant—mass lesions irregular or spiculated; breast architecture distorted; microcalcifications;
asymmetric; new or growing; skin thickening; nipple retraction; edema; increased density; malignant calcifications
clustered, multiple, tiny, and branched (benign calcifications tend to be solitary or scattered, bigger, round, and
monomorphic); order Eklund view or displaced view for women with breast implants
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| Cysts: make sure patient has simple cyst; complex cyst or internal septations can indicate carcinoma; needle aspiration—
patient has simple cyst if fluid not bloody and mass goes away and does not recur in 2 to 3 wk; work up patients with
bloody fluid
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| Biopsy: negative results of fine needle aspiration cytology can be due to geographic miss (core needle biopsy preferred and
accurate); excisional biopsy common; use core needle biopsy for nonpalpable lesions; avoid surgical biopsy for diagnosis;
stereotactic core machine reliably and safely indicates where needle should be inserted in patients with nonpalpable
mammographic abnormality
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| MRI of breast: becoming increasingly popular; expensive; shows cross-sectional anatomy of breast; no radiation; highly
sensitive but not highly specific; difficult to perform biopsy on patients with MRI abnormality; order US in patients with
MRI abnormality (if abnormality not visible with US, probability of malignancy 2%-3%; follow patients); useful for patients
with abnormal mammographic finding not clearly mass (eg, asymmetric density); sometimes used for high-risk
screening; order MRI implant study for patients with ruptured implant
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| Work-up of postmenopausal woman with palpable mass: clinically malignant—mammography; US to determine
whether patient has cyst (cysts rare in postmenopausal women not on hormones); needle biopsy; counsel patient; not obviously
malignant—mammography and US; biopsy; nonmalignant masses in postmenopausal women rare
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| Work-up of premenopausal woman with palpable mass: clinically malignant—mammography; US; excise masses if
fine needle biopsy findings benign; core needle biopsy preferred; if findings malignant, give preoperative counseling and
education; not clinically malignant—mammography; US; consider fibroadenoma or fibrocystic disease; perform biopsy
or reexamine patient in 2 mo (if mass persists, perform biopsy; if mass resolves, routine follow-up required)
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| Case presentations: woman 43 yr of age—silicone implants firm from aging (examination and mammography difficult);
mother died from breast cancer at age 75 yr (imparts little increased risk); no history of breast problems or use of hormones;
firm 1-cm mass in upper outer quadrant of left breast; lymph nodes negative; mammography and US negative but
excisional biopsy or needle biopsy required; woman 50 yr of age—right breast cancer treated with lumpectomy and irradiation
3 yr ago; edema on right breast looks like peau d'orange (expected after irradiation); left breast normal; mammography
shows architectural distortion at site of previous lumpectomy which has worsened since previous
mammography; work-up should include biopsy (excisional biopsy acceptable; sterotactic biopsy machines not sensitive
enough for architectural distortions); US not good for scars; MRI good; woman 22 yr of age—firm mobile mass in upper
outer quadrant of breast; regional lymph nodes negative; mammography not useful in women <30 yr of age, and excisional
biopsy usually not performed; MRI expensive; fine needle aspiration cytology or core biopsy recommended
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| Questions and answers: documenting “mass”—mass implies dominant mass unlike any other mass; differentiate mass
from diffuse nodularity; document symmetry; work up masses
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| PMS: RECOGNITION AND MANAGEMENT —Andrea Rapkin, MD, Professor of Obstetrics and Gynecology, David
Geffen School of Medicine at the University of California, Los Angeles
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| Distinguishing premenstrual symptoms from depression: less functional impairment and fewer mood symptoms with premenstrual
syndrome (PMS), compared to premenstrual dysphoric disorder (PMDD), depression, and dysthymia; physical
symptoms (eg, breast tenderness and bloating) characteristic of PMS and PMDD but not depression; depression and dysthymia
associated with change in appetite, fatigue, lethargy, and sleep disorder; PMDD symptoms resolve within days of onset of
menses and with pregnancy; premenstrual symptoms return within 1 to 2 cycles if treatment with selective serotonin reuptake
inhibitor (SSRI) discontinued (remission persists after discontinuing treatment for depression)
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| Diagnosis: criteria for PMDD—diagnosis requires ≥5 symptoms and ≥1 severe mood symptom; symptoms include irritability,
mood swings, depression, tension, anxiety, and physical symptoms; symptoms must interfere markedly with work, school,
or usual relationships and must not be exacerbation of underlying depressive disorder; confirm criteria for 2 consecutive cycles;
take careful history; perform physical examination to rule out diabetes, thyroid disease, anemia, chronic fatigue syndrome, connective
tissue disease, pain problems (eg, endometriosis), substance abuse, and psychiatric disorders; ask about previous episodes
of depression or uncontrolled physical activity (eg, manic episode lasting >2 wk that was not premenstrual); refer for
psychiatric interview if indicated; establish severity and luteal cyclicity; use diary; complete blood count (CBC) for women
with heavy periods; pain other than breast tenderness not characteristic of PMDD (pelvic pain and premenstrual pain more consistent
with congestive dysmenorrhea and secondary dysmenorrhea); new onset at 40 to 50 yr of age unusual (obtain day 3 follicle-stimulating
hormone [FSH] level [>12 mIU/mL consistent with waning of ovarian function, >20 mIU/mL consistent with
menopause]); perimenopausal symptoms tend to be present during entire month
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| Interference with daily functioning: PMDD interferes with daily function (PMS probably does not); PMDD impairs family
and social activities at level of depression
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| Management: diary—ask patient to rate 5 worst symptoms from 0 to 3 (ie, none, mild, moderate, severe) for each day of
menstrual cycle for 2 cycles prospectively; mild symptoms often resolve with conservative measures; explain to patients
severe symptoms require appropriate diagnosis; after 2 mo, provide more involved therapy if indicated
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| Potential therapy: holistic therapy—no good evidence for magnesium; 1200 mg of calcium carbonate in divided doses
throughout month not shown problematic (in patients who do not have renal stones); minimal effectiveness of vitamin E
questionable; high doses of vitamin B6 can result in irreversible motor neuropathy (<100 mg daily recommended); limited
studies about L-tryptophan; diet and exercise—studies found snack of simple carbohydrates and small amount of protein
improved mood; L-tryptophan more likely to cross blood-brain barrier if no competition from other proteins present; exercise
improves physical symptoms; low-fat vegetarian diet associated with reduction of symptoms; cognitive behavioral
therapy (CBT)—effective; costly; 12 wk of individual CBT superior to waitlist for psychologic and physical symptoms;
can be as effective as SSRI for treatment of depression; includes stress reduction and relaxation techniques, massage, anger
management, self-help, couples therapy, light-box therapy, and biofeedback; chaste tree berry (Vites agnus castus) may decrease
libido
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| Treatment of moderate to severe premenstrual symptoms: citalopram, fluoxetine, and paroxetine undergoing trials; fluoxetine,
paroxetine, and sertraline (Zoloft) approved by Food and Drug Administration (FDA); antidepressants that increase
dopamine and norepinephrine (eg, bupropion [Wellbutrin]) generally do not interfere with libido or cause weight gain, but
SSRIs more effective; bupropion not as effective as fluoxetine; maprotiline (tricyclic agent used in Europe) not available in
United States; taper paroxetine and venlafaxine (Effexor) before onset of period (tapering not required with longer-acting
SSRI or sertraline); starting therapy in luteal phase advantageous because of fewer side effects; use throughout cycle if patient
has underlying depressive disorder with premenstrual exacerbation; physical symptoms—improve more with fluoxetine
than with sertraline or paroxetine; higher-dose regimens of sertraline and paroxetine more effective on physical
symptoms; breast tenderness and bloating (but not headache) improve with treatment; luteal dosing 20 mg (some improvement
seen with 10 mg); luteal dosing of sertraline as effective as continuous dosing
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| Duration of medication: symptoms return when medications discontinued and remit when drugs restarted; treat for 1 yr and
stop if patient willing to stop; if symptoms recur, restart medication
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| Side effects: most improve over time; if symptoms related to insomnia, taking medication in morning and using less-activating
SSRI (eg, paroxetine) helpful; nervousness; restlessness; agitation; gastrointestinal (GI) symptoms; increased neonatal intensive
care unit admissions and respiratory symptoms when drug continued into third trimester of pregnancy; sexual dysfunction;
greater weight gain with paroxetine than with sertraline and fluoxetine
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| Sexual dysfunction: phosphodiesterase inhibitors (eg, sildenafil [Viagra], tadalafil [Cialis]) may improve symptomatology;
PMDD can cause abnormal sexual functioning in luteal phase; take careful history and distinguish baseline symptoms from
drug-related events; give lowest effective dose for shortest amount of time; try switching medications; increasing dopamine
may be helpful; appropriate pornography effective for improving libido; bupropion, amphetamine (eg, methylphenidate [Ritalin]),
amantadine, or buspirone (BuSpar) may be helpful; no good studies about ginkgo (Ginkgo biloba); cholinergic agonists
increase urinary urgency; no evidence for use of yohimbe in women
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| Advantages of SSRIs: can be discontinued if patient becomes pregnant (with little concern for teratogenicity); can be combined
with oral contraceptives without severely interfering with efficacy
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| Alprazolam: use for few days during luteal phase only, because of risk for dependence; taper to prevent withdrawal symptoms
when discontinuing; can cause fatigue
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| Hormonal therapy: medical oophorectomy (gonadotropin-releasing hormone [GnRH] agonist with add-back) useful when
uncertain whether severe premenstrual exacerbation due to depression, PMS, or PMDD; give trial of agonist to suppress
ovulation and give estrogen add-back (without progestin to prevent mood symptoms); check symptoms after 3 to 4 mo; if
patient does well and not interested in oophorectomy, continue regimen with estrogen add-back and trial of progestin add-
back (if progestin add-back intolerable, use progestin-secreting intrauterine device [IUD; Mirena]); hypoestrogenic side effects
(eg, cardiovascular disease) unpredictable; danazol prevents ovulation and may be useful in few patients who do well
and do not ovulate on 200 mg daily; oral contraceptives—drospirenone (Yasmin) decreases water retention and androgenic
side effects (eg, weight gain, acne); placebo response rate high (statistical significance questionable); improve response
to oral contraceptive by giving continuously to prevent hormone withdrawal events that trigger symptoms; do not
choose androgenic progestin; choose low-dose pill; do not use tricyclic agent; use for prolonged time (stop pill for 4 days
when spotting starts)
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| American College of Obstetricians and Gynecologists (ACOG) guidelines: PMS defined as one severe physical symptom
or one severe psychologic symptom; lifestyle changes recommended; oral contraceptive pills did not show efficacy;
GnRH agonists for women contemplating oophorectomy who are severely impaired and not able to be controlled on antidepressants
(followed by psychiatrist) or patient with severe endometriosis; SSRIs initial treatment of choice for severe PMS
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Educational Objectives
| The goal of this program is to educate the listener about management of the breast lump and premenstrual syndrome (PMS).
After hearing and assimilating this program, the participant will be better able to:
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 | 1. Evaluate breast abnormalities based on physical examination and clinical findings.
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| 2. Select appropriate breast imaging studies.
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| 3. Work up and counsel patients with clinically malignant breast masses.
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| 4. Distinguish premenstrual symptoms from symptoms of depression.
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| 5. Choose the most effective therapy for moderate to severe premenstrual symptoms.
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Discussed on This Program
Alprazolam [Xanax, Xanax XR, Niravam]
Amantadine HCl [Symmetrel]
Bupropion HCl [Wellbutrin, Wellbutrin SR, Zyban]
Buspirone HCl [BuSpar]
Calcium carbonate (several trade names)
Chaste tree berry (Vitex agnus castus)
Citalopram HBr [Celexa]
Danazol [Danocrine]
Drospirenone and ethinyl estradiol [Yasmin]
Estrogens, conjugated [Premarin, Premarin Intravenous]
Estrogens, esterified [Menest]
Estrogens, synthetic conjugated A [Cenestin]
Fluoxetine HCl [Prozac, Prozac Pulvules, Prozac Weekly, Sarafem, Sarafem Pulvules]
Ginkgo (Ginkgo biloba)
Levonorgestrel-releasing intrauterine system [Mirena]
L-tryptophan
Magnesium [Almora, Mag-200, Mag-G, Maginex, Maginex DS, Mag-Ox 400, Magonate, Magonate Natal, Mag-Tab SR,
Slow-Mag, Uro-Mag]
Maprotiline HCl [Ludiomil]
Methylphenidate HCl [Concerta, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin LA, Ritalin–SR]
Paroxetine HCl [Paxil, Paxil CR]
Progestin-only products [Ortho Micronor, Nor-QD, Ovrette]
Pyridoxine HCl (B6 ) [Aminoxin, Nestrex]
Sertraline HCl [Zoloft]
Sildenafil citrate [Viagra]
Tadalafil [Cialis]
Trimegestone (progestin)
Venlafaxine HCl [Effexor, Effexor XR]
Vitamin E (several trade names)
Suggested Reading
Andrus GM: Recent and future advances in the treatment of PMS, PMD, and menopause. IDrugs 4:1373, 2000; Chalabian
J et al: Comprehensive needs assessment of clinical breast evaluation skills of primary care residents. Ann Surg Oncol
5:166, 1998; Cheung KL et al: Palpable asymmetrical thickening of the breast: a clinical, radiological and pathological
study. Br J Radiol 74:402, 2001; Collyar DE: Breast cancer: a global perspective. J Clin Oncol 19:101S, 2001; Freeman
EW: Luteal phase administration of agents for the treatment of premenstrual dysphoric disorder. CNS Drugs 18:453, 2004;
Halbreich U et al: Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline. Expert Opin Pharmacother
4:2065, 2003; Houssami N et al: Fibroadenoma of the breast. Med J Aust 174:185, 2001; Johnson SR: Premenstrual
syndrome, premenstrual dysphoric disorder, and beyond: a clinical primer for practitioners. Obstet Gynecol 104:845,
2004; Khatun H et al: Correlation of fine needle aspiration cytology and its histopathology in diagnosis of breast lumps.
Bangladesh Med Res Counc Bull 28:77, 2002; Markopoulos C et al: Management of nonpalpable, mammographically
detectable breast lesions. World J Surg 23:434, 1999; Mehmood A et al: Role of cytological grading in the management of
breast lump. J Coll Physicians Surg Pak 13:150, 2003; Mitwally MF et al: Pharmacotherapy of premenstrual syndromes
and premenstrual dysphoric disorder: current practices. Expert Opin Pharmacother 3:1577, 2002; Parkyn R: Discovering
a breast lump. Management plans and pitfalls. Aust Fam Physician 22:43, 1993; Place R et al: Fine needle aspiration in
the clinical management of mammary masses. Surg Gynecol Obstet 177:7, 1993; Steiner M et al: Diagnosis and treatment
of premenstrual dysphoric disorder: an update. Int Clin Psychopharmacol 15 Suppl 3:S5, 2000; Strine TW et al: Menstrual-related
problems and psychological distress among women in the United States. J Womens Health (Larchmt)
14:316, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Rapkin is on the Speakers’ Bureau for TAP Pharmaceuticals and Pfizer US Pharmaceutical Group.
Drs. Giuliano and Rapkin spoke at the 32nd Annual Family Practice Refresher Course, presented May 31 to June 4,
2005, by the David Geffen School of Medicine at the University of California, Los Angeles. The Audio-Digest Foundation
thanks the speakers and the David Geffen School of Medicine at UCLA for their cooperation in the production
of this program.
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