Edward D.

Kim, MD

Background
A 58-year-old construction site foreman presents with the chief complaint that he is unable to
maintain an erection. The onset was gradual; however, the problem has been progressing for
2 years. With sufficient stimulation, he can obtain a firm erection with a rigidity of
approximately 90%. He does not have difficulty with orgasm or ejaculation.
The patient is in a stable, monogamous relationship and has intercourse 2-4 times per month.
He does not believe that any significant underlying psychogenic factors are at work. The
erections do not improve with self-stimulation or in the morning.
Comorbid conditions include obesity, dyslipidemia, and hypertension. The patient also
smokes half a pack of cigarettes per day and does not exercise. His medications include a
statin and a calcium-channel blocker, both of which he has used for 5 years. He does not use
organic nitrates. His family history includes coronary artery disease.
A review of systems reveals an absence of chest pain or dyspnea upon exertion. The patient
has moderate lower urinary tract symptoms (LUTS), characterized by slow stream and
hesitancy, and he has mild urinary urgency. However, he does not have a sense of incomplete
bladder emptying. He is easily tired, especially in the afternoon, and his libido is mildly
decreased.

Physical Examination and Workup 

The examination reveals a virilized male with normal-sized testes. The prostate is moderately
enlarged but without evidence of induration or nodules. The penis is normal but is becoming
buried in suprapubic fat. No gynecomastia or lower-extremity edema is present. The
abdomen is obese but is soft, flat, and nontender.
The patient has a body mass index (BMI) of 32 kg/m 2, a blood pressure of 145/90 mm Hg,
and a heart rate of 80 beats/min. Pedal pulses are present.
Lipid levels are borderline high. The serum total testosterone level is 345 ng/dL (normal
range, 300-950 ng/dL). Basic metabolic profile findings are normal. A previous prostate-
specific antigen result was 2.1 ng/mL. The hematocrit was 45%. A brief neurologic
examination does not reveal any focal sensory or motor deficits.
The patient's erectile function (EF) domain score, as derived from the International Index of
Erectile Function (IIEF) questionnaire, is 19.

Discussion
The patient was diagnosed with organic erectile dysfunction (ED). Although organic and
psychogenic ED may be commonly seen together, the patient's smoking habit, obesity,
dyslipidemia, and hypertension are highly suggestive of an organic etiology.
After counseling from his physician, the patient decided to pursue aggressive lifestyle
modification with smoking cessation, diet, and exercise. At the same time, he decided to use
an oral phosphodiesterase type 5 inhibitor on a daily basis to treat both the ED and benign
prostatic hypertrophy (BPH). He was given an alternative treatment of an oral
phosphodiesterase type 5 inhibitor on an as-needed basis in combination with oral BPH
therapies, such as a selective alpha blocker or a 5 alpha-reductase inhibitor.
ED is defined as the inability to achieve or maintain an erection that is sufficient for sexual
intercourse. ED is only one type of male sexual dysfunction, however; on the basis of a
comprehensive history, ED should be distinguished from problems with orgasm, ejaculation,
genital pain, or libido
A low serum testosterone level may be seen men with ED. Many men become focused on
concern about low testosterone levels. However, most men who are administered testosterone
therapies do not have significant improvements in erectile function because comorbid
conditions are responsible for the ED. Morning total testosterone level, as well as serum
chemistries, complete blood count, lipid profile, and fasting blood glucose level, are typically
obtained at the initial evaluation. If the total testosterone level is low or borderline, a free or
bioavailable testosterone level and luteinizing hormone level should be measured.
BPH, also referred to as "LUTS," and ED are increasingly common with aging. A strong
association between these conditions was observed in the large-scale Multinational Survey of
the Aging Male (MSAM-7).[1] In this questionnaire-based survey, the prevalence of moderate
to severe LUTS was age-related, increasing from 22% in men aged 50-59 years to 45.3% in
men aged 70-80 years. The prevalence of ED also increased with age. The association
between LUTS and sexual dysfunction persisted after controlling for age and other
comorbidities known to affect sexual function.
Similarly, Seftel and colleagues analyzed studies that reported on the prevalence of coexistent
LUTS/BPH and ED using alternative scales for LUTS (ie, International Prostate Symptom
Score).[2] The average rates of coexisting conditions were 43% among men in their 40s, 72%
among men in their 50s, and 79% among men in their 60s.

ED and cardiovascular disease share similar underlying risk factors, including endothelial
dysfunction, blood vessel size, and androgen levels. Abnormalities of endothelial function are
closely linked with the metabolic syndrome, diabetes, hypertension, and dyslipidemia.
Thompson and colleagues' landmark study from the Prostate Cancer Prevention Trial
determined that ED can be an indicator of future morbidity and mortality, with the incident
development of ED being associated with a hazard ratio of 1.25 for future cardiovascular
events.[3]
In a separate study, Inman and colleagues followed men with ED and identified an 80%
increased risk of developing coronary artery disease after 10 years.[4] In younger men, ED
was associated with an increased risk for future cardiac events, while having little prognostic
significance in older men.
The Princeton Consensus Guidelines Panel recommended that men with ED undergo a full
medical assessment, with stratification of cardiovascular risk as high, medium, or low.
[5]
 High-risk men are those with unstable or refractory angina, a recent history of myocardial
infarction, certain arrhythmias, or uncontrolled hypertension. Figure 3 shows the risk factors
for patients with and without established cardiovascular disease.
Sexual activity with any particular ED therapy should be deferred until the cardiac condition
is stabilized for high-risk men, who should undergo cardiologic referral for cardiovascular
stress testing and subsequent risk reduction therapy. The patient in this case is classified as
having medium risk factors -- obesity, dyslipidemia, hypertension, and a family history of
cardiac disease -- and would benefit from cardiac stress testing.
Penile duplex ultrasonography, nocturnal penile tumescence tests, and penile angiography are
considered specialized tests for ED. They are not recommended for routine use, but are best
reserved for complicated or unusual cases in which they may affect selection of treatment.
The IIEF is a validated questionnaire that is widely used to characterize ED. The severity of
ED is classified into 5 diagnostic categories, as follows:
 No ED: IIEF score = 26-30
 Mild ED: IIEF score = 22-25
  Mild to moderate ED: IIEF score = 17-21
 Moderate ED: IIEF score = 11-16
 Severe ED: IIEF score = 6-10
The association of modifiable behavioral factors with ED, primarily among men free of
comorbidities, underlies the rationale for intervention. These strategies have been proposed to
prevent and potentially improve erectile function. Because nitric oxide is the key factor in
vascular health, ED, and cardiovascular disease, the focus has been on measures to increase
vascular nitric oxide production.

Suggested mechanisms by which weight loss, healthy diet, and physical exercise can
improve ED include the amelioration of endothelial dysfunction, insulin resistance, and a
low-grade inflammatory state associated with diabetes and metabolic diseases, all of which
are risk factors for ED. The resulting improved inflammatory status may contribute to
reducing the burden of sexual dysfunction in men.
Lifestyle changes, such as increased physical activity, healthy diet, and reduced caloric
intake, have been associated with the improvement of ED in the general male population.
In a landmark study, Esposito and colleagues conducted a randomized controlled trial
involving 110 obese men with ED.[6] Men assigned to the intervention group were entered
into an intensive weight-loss program involving personalized dietary and exercise counseling.
Men in the control group were given general oral and written information about healthy food
choices and exercise but were not placed in specific, individualized programs.
After 2 years, men assigned to the intervention group lost significantly more weight,
increased their physical activity, experienced favorable changes in physiologic measures of
endothelial dysfunction, and had significant improvement in their ED score compared with
men in the control group. Moreover, the number of men without ED was significantly higher
in the group assigned to intensive lifestyle changes than in the control group.
Similar conclusions were reached in a group of diabetic men. Wing and colleagues studied 1-
year changes in ED in 306 overweight men with type 2 diabetes mellitus participating in the
Look AHEAD trial.[7] At 1 year, 8% of men assigned to the intensive lifestyle intervention
reported worsening of erectile function, compared with 22% of the control participants. The
overall IIEF domain score improved from 17.3 to 18.6 in the intervention group.

1. Rosen R, Altwein J, Boyle P, et al. Lower urinary tract symptoms and male sexual
dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol.
2003;44:637-49. Source
2. Seftel AD, de la Rosette J, Birt J, Porter V, Zarotsky V, Viktrup L. Coexisting lower
urinary tract symptoms and erectile dysfunction: a systematic review of
epidemiological data. Int J Clin Pract. 2013;67:32-45. Source
3. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman
CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA.
2005;294:2996-3002. Source
4. Inman BA, Sauver JL, Jacobson DJ, et al. A population-based, longitudinal study of
erectile dysfunction and future coronary artery disease. Mayo Clin Proc. 2009;84:108-
13. Source
5. Nehra A, Jackson G, Miner M, et al. The Princeton III consensus recommendations
for the management of erectile dysfunction and cardiovascular disease. Mayo Clin
Proc. 2012;87:766-78. Source
 6. Esposito K, Giugliano F, Di Palo C, et al. Effect of lifestyle changes on erectile
dysfunction in obese men: a randomized controlled trial. JAMA. 2004;291:2978-
84. Source
7. Wing RR, Rosen RC, Fava JL, et al. Effects of weight loss intervention on erectile
function in older men with type 2 diabetes in the Look AHEAD trial. J Sex Med.
2010;7(1 Pt 1):156-165.
8. Burnett AL, Nehra A, Breau RH, et al. Erectile dysfunction: AUA Guideline
(2018). Source

A 43-Year-Old Man With Severe Itching and Hyperlipidemia

Melba Estrella, MD; John Plante; Andraia Li; Margaret LaPorte; Dirk M. Elston, MD

Background
A 43-year-old man presents to the dermatology clinic with a rash that affects both axillae.
The rash began about a week ago (Figure 1). He complains of severe, intense itching but
denies the presence of pain or burning. The patient states that he also has diffuse itching on
the trunk and extremities. His symptoms have progressively worsened.

He has no history of fever, chills, malaise, or recent travels. He reports no history of exposure
to known sick contacts, recent hiking, or outdoor activities. He is an accountant and lives
with his wife and two school-aged children who have not experienced similar symptoms or
rashes. He denies any recent changes in household detergents, soaps, or shampoos.
He acknowledges that he is overweight and had signed up for a weight-loss workout program
3 weeks ago. Despite expressing his discomfort about having to wear workout clothes, he has
experienced significant progress in mood and energy levels. However, his intense itching is
substantially decreasing his quality of sleep.
He has no family history of eczema or asthma. His past medical history is significant
for chickenpox in childhood and seasonal allergic rhinitis. Several months ago, he was
diagnosed with hyperlipidemia for which he received simvastatin therapy. His other current
medications include fluticasone nasal spray as needed and ibuprofen for occasional joint pain.

Physical Examination and Workup

Upon physical examination, the patient is a well-appearing middle-aged man with
an obese physique. His vital signs include a temperature of 98.3°F (36.8°C), blood pressure
of 142/83 mm Hg, a respiratory rate of 15 breaths/min, and a heart rate of 87 beats/min.
He has mild conjunctival injection bilaterally. His nasal mucosa is pale with clear rhinorrhea.
He has a regular heart rhythm with no murmurs or gallops. His respirations are nonlabored,
and his breath sounds are clear to auscultation bilaterally. Upon abdominal examination,
truncal obesity is observed. His abdomen is soft and nontender with normal bowel sounds.
Neurologic examination findings are normal.
Skin examination reveals multiple erythematous papules that coalesce, forming poorly
demarcated plaques confined to friction areas on the posterior border of both axillary folds,
with sparing of axillary vaults. Few excoriations with overlying sanguineous crusting are
present. Lips, oral mucosa, and nails are unaffected.
Discussion
This patient's clinical presentation is consistent with allergic contact dermatitis due to
clothing. The appearance of an eczematous eruption involving the periphery of the axillary
vault suggests textile contact dermatitis. Tightly covered posterior axillary folds are subject to
friction and perspiration. Perspiration in the absence of evaporation may lead to dye leakage
from fabrics, triggering allergen sensitization. [1,2] The axillary vault is typically involved in
deodorant dermatitis, whereas the periphery of the vault suggests clothing dermatitis.
Clothing dermatitis may be caused by dyes or resins within the fabric.
Patch testing was performed and revealed positive reactions to resins used in textile
manufacturing. The remaining differential diagnoses presented were excluded based on the
patient's history and physical examination findings. The key factor that pointed away from a
diagnosis of deodorant contact dermatitis was the distribution of the rash. In this patient, the
axillary vault was spared. Although deodorant contact dermatitis is also a form of allergic
contact dermatitis, and therefore may appear with a similar morphology, this diagnosis would
be more likely if the patient's axillary vault was affected.[3]
Although textile contact dermatitis may mimic atopic dermatitis, this condition
characteristically involves the flexor surfaces in adults. In addition, adults with atopic
dermatitis typically have a history of childhood eczema.[4]
This patient occasionally takes ibuprofen, a medication that is commonly implicated in fixed-
drug eruptions. However, a progressively darkening, erythematous, and sharply demarcated
oval patch that recurs at the same skin sites with each exposure would be expected. Also,
eruptions secondary to the use of nonsteroidal anti-inflammatory drugs commonly involve
the oral mucosa.[3,4] Although this patient does have a history of chickenpox, herpes zoster is
less likely to be the diagnosis because it typically appears as a painful vesicular rash that
follows a unilateral dermatomal distribution.[4]
Contact dermatitis can be divided into irritant and allergic contact dermatitis. The
inflammatory response in irritant contact dermatitis does not require prior sensitization and is
due to nonimmune mediated mechanisms.[4,5] Examples of irritants include acids, alkalis, and
detergents.[3,4] Numerous substances, including neomycin, formaldehyde, and poison ivy, can
cause allergic contact dermatitis. Prior sensitization to an allergen is required because the
pathogenesis involves a cell-mediated delayed (type IV) hypersensitivity reaction.[3] Textile
contact dermatitis is a subtype of allergic contact dermatitis.

Textiles are any kind of fabric formed by natural and synthetic fibers or a combination of
both.[6] Most fibers themselves rarely cause immune-mediated sensitization, whereas the
primary cause of textile allergy arises from textile preparation and its treatment processes.
The most common sensitizing agents include dyes, finishing resins, and rubber additives.
These substances serve the functions of improving clothing durability and appearance.
Several finishing chemicals, including urea-formaldehyde and melamine-formaldehyde, have
been used for decades to prevent wrinkles. These compounds trigger sensitization because
formaldehyde eludes from the bound fibers.[6] Textile dyes are by far the most common
overall cause of textile contact dermatitis.[1,7] In a study of 154 patients with textile contact
dermatitis, dyes accounted for 79.8% of all positive results on patch tests. [1] Approximately
13% of the cohort was sensitized to several compounds that included rubber additives,
whereas the remainder were allergic to formaldehyde and finishing resins.
Reactive dyes are primarily used to color the natural fiber found in cotton, wool, and silk.
Sensitization to these dyes are quite rare. [6] Disperse dyes are commonly used to dye synthetic
fabrics, such as polyester, acetate, nylon, and fiber mixtures, and they account for more than
20% of all dyes. The prevalence of allergy to these dyes is estimated to be 0.4% to 6.7% and
includes dyes such as disperse blue 106, disperse blue 124, and disperse yellow 3. [1,8] These
dyes only partially bind to textile fibers, possibly explaining their strong sensitizing
properties. Furthermore, their propensity to leak from fabric increases in the presence of
friction and moisture, thereby enhancing their immunogenic potential.[6,7]
Due to the wide variety of textiles, numerous body areas may be involved. Thus, distribution
is a crucial diagnostic clue to the identity of the sensitizing compound. [3] Textile contact
dermatitis typically appears in the fifth decade in women and fourth decade in men. Textile
contact dermatitis may mimic or exacerbate atopic dermatitis if the antecubital or popliteal
fossae are involved. A higher incidence of textile contact dermatitis is also observed in those
with a prior history of atopic dermatitis because disruption of the skin barrier increases the
likelihood of sensitization.[1,2] Secondary infection is common.[3]
The clinical presentation can range from an acute flare with erythema and vesicles to chronic
manifestations such as lichenification. [5] In a study of 211 patients, most (79.9%) had a
pruritic eczematous dermatitis with oozing vesicles; 20% of patients had atypical
presentations including lichenoid, purpuric, lymphomatoid, psoriasiform, pustular, and
nummular variations.[1] Most patients (95.3%) in a 277-patient cohort also had eczematous
eruptions, and the remainder (4.7%) had atypical presentations.[1]
Body areas subject to heat, friction, and sweating are more likely to experience sensitization.
[2]
 The neck, trunk, abdomen, lower limbs, and axillary folds, where clothing is often tight,
are common locations of nonoccupational textile contact dermatitis. Occupational textile
contact dermatitis due to dyeing practices most commonly involves the hands. However, the
eyelids, abdomen, and upper limbs may be involved as well. No evidence to date suggests a
correlation between the clinical pattern and distribution of textile contact dermatitis and the
responsible allergens.[1]
Due to the diverse manifestations of textile contact dermatitis, the differential diagnosis is
broad and may include dyshidrotic eczema, atopic dermatitis, tinea corporis, inverse
psoriasis, scabies, palmoplantar psoriasis, nummular dermatitis, seborrheic dermatitis, irritant
contact dermatitis, and other causes of allergic contact dermatitis.[5] Eczematous drug
eruptions caused by calcium channel blockers can be widespread on the trunk and extremities
but are usually not accentuated at the periphery of the axillary vault. This is also true of
allergy to cocamidopropyl betaine in soaps and body washes.
A high index of suspicion is warranted. The diagnosis is often suggested by a detailed history
and physical examination. If textile contact dermatitis is suspected, the next step is to obtain
patch testing, which is confirmatory in the appropriate clinical context. [3,9] In patients with
suspected textile contact dermatitis, supplementing the standard panel with the textile dyes
may be helpful.[6] A suspected fabric may also be placed under a patch for 3-4 days.[3]

The management of textile contact dermatitis involves treatment of the acute flare and patient
education. Medical management of localized acute textile contact dermatitis includes a mid-
potency or high-potency topical steroid or calcineurin inhibitor.[4,5] Cool compresses may be
used to reduce acute symptoms. Emollients or barrier creams may help limit allergen
exposure.[5] In acute, severe, generalized cases, a short course of systemic steroids may be
used.[4,5]
Locating and removing contactants from the patient's environment are critical to successful
management. Part of patient education includes a discussion of compound cross-reactivity.
Avoiding certain colors in clothing may not necessarily be effective because many colors are
composed of a mix of dyes. Instead, wearing clothing made with nonsynthetic fibers is
advised.[7] Washing new clothing twice prior to first wear is recommended.[3]
This patient in this case was prescribed triamcinolone 0.1% cream and advised to wear 100%
cotton or synthetic clothing during exercise. With this treatment, his symptoms greatly
improved, as described at his follow-up appointment 1 month later.
 1. Lisi P, Stingeni L, Cristaudo A, et al. Clinical and epidemiological features of textile
contact dermatitis: an Italian multicentre study. Contact Dermatitis. 2014;70:344-
350. Source
2. Mowad CM, Anderson B, Scheinman P, et al. Allergic contact dermatitis: patient
management and education. J Am Acad Dermatol. 2016;74:1043-1054. Source
3. James, WD, Elston, DM, Treat, JR, Rosenbach, MA, Neuhaus, IM. Andrews'
Diseases of the Skin: Clinical Dermatology. 13th ed. Elsevier; 2020:92-102,120-1.
4. Marks JG, Miller JJ. Lookingbill & Marks' Principles of Dermatology. 6th ed.
Elsevier; 2019:95-102,141-143, 221.
5. Usatine RP, Riojas M. Diagnosis and management of contact dermatitis. Am Fam
Physician. 2010;82:249-255. Source
6. Svedman C, Engfeldt M, Malinauskiene L. Textile contact dermatitis: how fabrics can
induce dermatitis. Curr Treat Options Allergy. 2019;6:103-111. Source
7. Malinauskiene L, Bruze M, Ryberg K, Zimerson E, Isaksson M. Contact allergy from
disperse dyes in textiles: a review. Contact Dermatitis. 2013;68:65-75. Source
8. Nygaard U, Kralund HH, Sommerlund M. Allergic contact dermatitis induced by
textile necklace. Case Rep Dermatol. 2013;5:336-339. Source
9. Mowad CM, Anderson B, Scheinman P, Pootongkam S, Nedorost S, Brod B. Allergic
contact dermatitis: patient diagnosis and evaluation. J Am Acad Dermatol.
2016;74:1029-1040. Source

A 56-Year-Old Teacher With Worsening Hip Pain

Avan Armaghani, MD

Background
A 56-year-old woman with no significant past medical history presents with left hip pain. She
began experiencing this pain about 4 months ago. She says that she initially noticed the pain
when she was walking and that it would resolve with rest.
She saw a chiropractor and physical therapist but experienced only minimal relief. The pain
then became progressively worse, and she began experiencing it at rest. She rates the pain as
"8 out of 10" on a pain scale. She describes it as achy and localized in the left hip. The pain
does not radiate down her leg. She denies any stiffness feeling in her hips.
The patient has taken over-the-counter pain relievers, which temporarily reduce the pain to "5
out of 10" on a pain scale. She has never experienced a similar sensation. She does not report
any weakness, numbness, or tingling sensation in her legs. She has not had any recent trauma.
She does not have fever, chills, blurry vision, double vision, cough, chest pain, shortness of
breath, nausea, vomiting, or abdominal pain.
The patient is otherwise healthy and does not take any other medications beyond the
aforementioned pain relievers. She works as a third-grade teacher. She denies smoking and or
drinking alcohol. She is postmenopausal. She has a family history significant for a maternal
aunt who was diagnosed with breast cancer at age 45 years and underwent surgery,
chemotherapy, and radiation treatment. The patient does not have any other family history of
breast cancer, ovarian cancer, or other cancer.

Physical Examination and Workup

Upon physical examination, the patient's vital signs include blood pressure of 140/90 mm Hg,
pulse of 85 beats/min, temperature of 98.3°F (36.8°C), respiration rate of 15 breaths/min, and
weight of 189 lb (85.7 kg).
Her mental status appears normal. She is alert and oriented and is sitting comfortably, with no
acute distress. Her pupils are symmetric and reactive to light. Her extraocular movements are
intact. Her conjunctivae are normal. Her cardiac, pulmonary, abdominal, and musculoskeletal
examination findings are otherwise unremarkable.
She has normal muscle bulk and tone and normal upper- and lower-extremity strength. She
has no swelling or no deformities. She has no pain with compression of the left or right hip.
Her sensation is intact bilaterally. She has 5/5 strength in hip flexion and extension, knee
flexion and extension, and ankle dorsiflexion and plantar flexion bilaterally. Results of a
straight leg test are negative bilaterally. Her gait is normal.
The results of her complete blood cell count with differential and comprehensive metabolic
panel are within normal limits.

Discussion
The patient did not report any recent trauma, and her gait is normal, which makes hip fracture
unlikely. She did not experience radiation of pain down her leg, and results of a straight leg
test were negative, which points away from sciatica. Finally, the patient is younger than 60
years, and her pain initially occurred with activity but then eventually occurred with rest as
well; this makes osteoarthritis unlikely.
The patient underwent radiography of the left hip. This revealed a lytic lesion at the left
proximal hip approximately one half to two thirds the cortical width, adjacent to the medial
calcar and lesser trochanter. Follow-up MRI of the left hip with contrast revealed a 3 × 2 cm
lesion in the peritrochanteric region of the left proximal femur.
The patient underwent left femur biopsy, which revealed metastatic adenocarcinoma
consistent with primary breast cancer. She subsequently underwent PET, which showed a
fluorodeoxyglucose-avid right breast mass and diffuse bony metastatic disease. She had no
evidence of visceral involvement. Follow-up bilateral mammography was performed and
revealed an irregular mass in the right breast. A similar example is shown in the figure below.

MRI of the breast revealed multiple irregular masses throughout all four quadrants of the
right breast, spanning at least 8.5 × 6.4 × 8.4 cm in total extent. A breast examination was not
conducted during the patient's initial physical examination because breast cancer was not
immediately suspected as a cause. A biopsy of the right breast mass revealed invasive ductal
carcinoma ER 100%/PR 95%/HER2 negative (Figure 2).

This case is an example of a patient with breast cancer who first presented after metastasis.
De novo metastatic breast cancer accounts for as many as 5% of all new breast cancer
diagnoses.[1] In addition, as many as 30% of patients with early-stage cancer at presentation
develop metastatic disease. The clinical presentation of metastatic breast cancer varies and
depends on the organs that are involved. For example, metastatic disease to the lungs can
present as cough or shortness of breath. Abdominal pain, nausea, or jaundice can suggest
liver involvement. Persistent back or hip pain can suggest bone involvement.[2]
In this case, the patient presented with oligometastatic disease, with one site of metastatic
disease in the left femoral neck. As many as 10% of newly diagnosed metastatic breast cancer
cases present with oligometastatic disease.[2] An aggressive approach to treatment is
oftentimes considered in an attempt to achieve cure.[3] This requires a multidisciplinary
approach that includes surgery, radiation oncology, and medical oncology.
Although hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer
cannot be cured, recent scientific advancements in therapies have provided significant
improvements in prolonging patient lives and maintaining a good quality of life. Various
strategies are used in treatment of metastatic breast cancer in postmenopausal women. The
first involves eliminating the production of estrogen with aromatase inhibitors (AIs), which
include anastrozole, letrozole, and exemestane. Tamoxifen improved breast cancer recurrence
and mortality by 30%-40% compared with placebo in a meta-analysis that included trials
with both premenopausal and postmenopausal women.[4]
Although AI monotherapy is not the preferred first-line therapy in postmenopausal women
with HR+/HER2- metastatic breast cancer, it can be used in selected patients who may not be
able to tolerate other combination treatment regimens. A meta-analysis showed that AI
monotherapy had a statistically significant survival benefit in postmenopausal women
compared with tamoxifen and other endocrine therapies.[4]
The development of targeted therapies, including cyclin-dependent kinase (CDK) 4/6
inhibitors and mammalian target of rapamycin (mTOR) inhibitors, have transformed the
treatment of HR+/HER2- metastatic breast cancer. Palbociclib, ribociclib, and abemaciclib
are the three CDK 4/6 inhibitors currently approved by the US Food and Drug
Administration. Palbociclib in combination with an AI as first-line therapy in the treatment of
estrogen receptor-positive (ER+)/HER2- metastatic breast cancer has shown to have a
significant improvement in progression-free survival (PFS).[5] Similar findings have also been
found with ribociclib and abemaciclib.[6,7]
Given the significant improvement in PFS with CDK 4/6 inhibitors in combination with AI,
this is the preferred first-line treatment in metastatic ER+/HER2- metastatic breast cancer.
Fulvestrant is an alternative to first-line treatment for HR+/HER2- metastatic breast cancer.
[8]
 This is a selective estrogen degrader and has shown to be effective as monotherapy and in
combination therapy in the treatment of metastatic breast cancer.[9] Fulvestrant in combination
with ribociclib has shown improved PFS in patients with HR+/HER2- metastatic breast
cancer who have not received any prior treatment or as much as one line of prior endocrine
therapy.[10] The mTOR inhibitor everolimus, in combination with exemestane, has shown to
improve PFS in patients with HR+/HER2- metastatic breast cancer who were previously
treated with nonsteroidal AI.[10]
Subsequent lines of therapy in HR+/HER2- metastatic breast cancer include abemaciclib,
which has been shown to be effective monotherapy in patients whose disease progressed on
or after prior endocrine therapy and who had one or two chemotherapy regimens.
[11]
 Abemaciclib has also shown to have overall survival benefit in combination with
fulvestrant for women with disease progression after endocrine therapy.[12]
Chemotherapy remains an acceptable treatment option; however, with the advent of effective
nonchemotherapy treatment modalities that are associated with fewer side effects,
chemotherapy is generally used in much later lines of treatment.

The treatment of breast cancer continues to evolve, and therapies are becoming more
personalized. For example, oral poly(adenosine diphosphate-ribose) polymerase (PARP)
inhibitors are approved in the treatment of HER2- metastatic breast cancer in women who
harbor a germline BRCA mutation and have received prior lines of therapy. Olaparib and
talazoparib are PARP inhibitors that have been approved in this setting. [13,14] Patients who
harbor germline mutation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) and
who have previously received endocrine therapy but not chemotherapy are eligible to receive
a novel therapy, alpelisib, in combination with fulvestrant.[15]
Current National Comprehensive Cancer Network (NCCN) guideline category 1
recommendations for the treatment of HR+/HER2- metastatic breast cancer include AI plus a
CDK4/6 inhibitor, fulvestrant with or without an AI, and fulvestrant plus a CDK 4/6
inhibitor.[16] Category 1 recommendations for second and subsequent lines of therapy include
fulvestrant plus a CDK4/6 inhibitor, if a CDK 4/6 inhibitor has not previously been used.
Other considerations for second and subsequent lines of therapy include single-agent
fulvestrant, AIs, and targeted agents.
The patient in this case received radiation therapy to the left femur for palliative pain control.
She was then started on a combination of palbociclib and letrozole. PET was performed 3
months after initiation of treatment and showed treatment response.

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