Breast Cancer-1

Q1. A 42-year-old woman with BRCA1 mutation asks about strategies to reduce her risk of breast cancer. Which option provides the greatest risk reduction?

For a 42-year-old woman with a BRCA1 mutation, prophylactic bilateral mastectomy provides the greatest risk reduction.

The overall hierarchy of effectiveness for breast cancer risk reduction in this population is:

1. Prophylactic bilateral mastectomy.
2. Risk-reducing salpingo-oophorectomy.
3. Chemoprevention (such as tamoxifen or raloxifene).

It is important to note that for BRCA1 carriers specifically, subset analyses indicate that tamoxifen does not reduce the incidence of breast cancer, whereas it does provide a benefit for BRCA2 carriers and the general high-risk population.

Q2. A 55-year-old woman with stage II HER2+ breast cancer is planned for neoadjuvant therapy. Which regimen is guideline-preferred?

For a 55-year-old woman with stage II HER2+ breast cancer, the guideline-preferred neoadjuvant regimen is anthracycline-based chemotherapy (AC) followed by a taxane plus trastuzumab and pertuzumab (AC-THP).

Regimen Composition and Sequencing

Neoadjuvant therapy for HER2-positive disease typically utilizes a dual-HER2 blockade to maximize the probability of a pathologic complete response (pCR). The treatment is administered in a specific sequence to mitigate toxicity:

• Anthracycline Phase: Consists of doxorubicin and cyclophosphamide (AC).
• Taxane + HER2 Phase: Following AC, the patient receives a taxane (such as paclitaxel or docetaxel) in combination with trastuzumab and pertuzumab.
• Toxicity Precaution: Trastuzumab and pertuzumab are not given concurrently with anthracyclines due to a significantly increased risk of cardiotoxicity; instead, they are initiated during the taxane portion of the regimen.

Rationale for the Neoadjuvant Approach

Neoadjuvant systemic therapy is preferred for HER2-positive disease that is clinically stage II or higher for several reasons:

• Surgical De-escalation: It can shrink the primary tumor, potentially allowing a patient who was a candidate for a mastectomy to undergo breast-conserving surgery (BCS) instead.
• Prognostic Value: Determining the pCR at the time of surgery is a vital prognostic indicator, as patients who achieve pCR have better long-term outcomes.
• Modification of Adjuvant Therapy: If residual invasive disease is found at surgery after neoadjuvant therapy, guidelines recommend switching the patient to ado-trastuzumab emtansine (T-DM1) for 14 cycles, which has been shown to improve invasive disease-free survival compared to continuing trastuzumab.

Monitoring Requirements

Because these regimens carry a risk of reversible cardiomyopathy, LVEF monitoring via ECHO or MUGA is required at baseline and every 3 months during therapy. If the LVEF drops below 50% with an absolute decrease of $\ge$ 10% from baseline, HER2-targeted therapy should be held.

Q3. A 40-year-old premenopausal woman with ER+/HER2– breast cancer requires adjuvant endocrine therapy. What is the best option?

The preferred adjuvant endocrine therapy for a premenopausal woman is Tamoxifen for 5 years, with or without ovarian ablation or suppression (OAS).

Key considerations for choosing her regimen include:

• Risk Profile: Combined therapy (OAS plus Tamoxifen or an Aromatase Inhibitor) is strongly considered for patients at a higher risk of recurrence, such as those with lymph node involvement, high-grade tumors, or young age.
• AI Use: An Aromatase Inhibitor (AI) should only be used in premenopausal women if it is combined with OAS.
• Duration: Initial therapy typically lasts 5 years, after which additional treatment is considered based on her menopausal status at that time.

Q4. After neoadjuvant trastuzumab-based therapy, a patient has residual HER2+ disease at surgery. What is the preferred adjuvant therapy?

For a patient with residual HER2+ disease after neoadjuvant trastuzumab-based therapy, the preferred adjuvant treatment is ado-trastuzumab emtansine (T-DM1).

Key details regarding this recommendation include:

• Standard Regimen: The guideline-preferred duration is 14 cycles of T-DM1.
• Evidence: This strategy is based on the KATHERINE trial, which demonstrated significantly improved invasive disease-free survival (iDFS) with T-DM1 compared to continuing trastuzumab in patients with residual invasive disease at the time of surgery.
• Management of Toxicity: If T-DM1 must be discontinued due to toxicity, clinicians should administer trastuzumab +/- pertuzumab to complete a total of one year of HER2-targeted therapy.

Q5. A patient with ER+/HER2– metastatic breast cancer progresses on letrozole. What is the next systemic therapy?

For a patient with ER+/HER2– metastatic disease who progresses on an aromatase inhibitor like letrozole, the preferred next systemic therapy is to add a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) to fulvestrant. This strategy is generally reserved for patients who have not previously received a CDK4/6 inhibitor.

If the patient has already received a CDK4/6 inhibitor or if specific biomarkers are present, the following targeted options are recommended:

• PIK3CA mutation: Alpelisib plus fulvestrant is a preferred category 1 recommendation for postmenopausal patients.
• ESR1 mutation: Elacestrant monotherapy is indicated for patients with disease progression following at least one line of endocrine therapy.
• AKT1, PTEN, or PIK3CA mutations: Capivasertib plus fulvestrant is a category 1 option for these specific activating mutations.
• Nonsteroidal AI resistance: The combination of everolimus and exemestane is a guideline-supported option for patients who progressed on letrozole or anastrozole.

Q6. Which patients are candidates for PARP inhibitors (olaparib, talazoparib) in breast cancer?

Candidates for PARP inhibitors, specifically olaparib and talazoparib, are primarily defined by their genetic status and disease setting:

• Genetic Requirement: Patients must have a germline BRCA1 or BRCA2 mutation. NCCN also notes they may be considered for those with somatic BRCA1/2 mutations or germline PALB2, though data is more limited.
• Metastatic Setting: They are preferred over taxanes for patients with HER2-negative metastatic disease. While approvals focus on HER2-negative status, NCCN supports their use for any metastatic subtype if a germline BRCA mutation is present.
• Adjuvant Setting (Olaparib only): Olaparib is a category 1 recommendation for one year of treatment in patients with high-risk, HER2-negative early breast cancer who have completed adjuvant chemotherapy and local therapy. This includes:
  • TNBC: Those with residual disease after neoadjuvant therapy or stage $\ge$ pT2/pN1 after adjuvant chemotherapy.
  • HR-Positive: Those with $\ge$ 4 positive lymph nodes after adjuvant chemotherapy or high-risk residual disease after neoadjuvant treatment.

Q7. A 45-year-old woman with PD-L1+ metastatic TNBC is starting first-line therapy. Which regimen is recommended?

For a 45-year-old woman with PD-L1 positive metastatic TNBC, the recommended first-line therapy is pembrolizumab plus chemotherapy.

This approach is a category 1, preferred recommendation based on the KEYNOTE-355 trial, which demonstrated a survival benefit specifically for patients with a PD-L1 combined positive score (CPS) $\ge$ 10. Preferred chemotherapy partners for this regimen include paclitaxel, nab-paclitaxel, or the combination of gemcitabine and carboplatin.

Q8. Which monitoring is required with trastuzumab therapy?

Monitoring for trastuzumab therapy focuses primarily on cardiac function due to the risk of reversible cardiomyopathy.

Cardiac Monitoring Schedule

According to the prescribing information, Left Ventricular Ejection Fraction (LVEF) should be assessed via ECHO (preferred) or MUGA scan on the following schedule:

• Baseline: Prior to starting treatment.
• During Treatment: Every 3 months.
• Upon Completion: At the end of the 1-year treatment course.
• Post-Treatment (Adjuvant): Every 6 months for at least 2 years following completion.

Intervention Thresholds

Clinicians must withhold trastuzumab for at least 4 weeks if any of the following occur:

• An absolute LVEF decrease of $\ge$ 16% from baseline.
• LVEF falls below the institutional limit of normal AND there is an absolute decrease of $\ge$ 10% from baseline.

If a dose is held, LVEF should be repeated at 4-week intervals until it recovers.

Q9. What are the major long-term risks of tamoxifen therapy?

The major long-term risks associated with tamoxifen therapy are endometrial cancer and venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis.

Other significant long-term risks and toxicities identified in the sources include:

• Thromboembolic Events: The risk of PE is significantly increased in women ≥ 50 years old.
• Uterine Cancers: In addition to endometrial cancer, tamoxifen is associated with an increased risk of uterine sarcoma in postmenopausal patients.
• Ocular Issues: Patients have an increased incidence of cataracts and may require cataract surgery.
• Ischemic Heart Disease: Long-term follow-up from the ATLAS trial showed an increased risk of ischemic heart disease with 10 years of therapy compared to 5 years.
• Bone Health (Premenopausal): While tamoxifen is bone-protective in postmenopausal women, it is associated with a decline in bone mineral density in premenopausal patients.

What are the differences between ado-trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan (T-DXd)?

While both are HER2-directed antibody-drug conjugates (ADCs), they differ significantly in their chemotherapy payloads, clinical indications, and safety concerns.

Mechanism and Payloads

• T-DM1 (ado-trastuzumab emtansine): Utilizes emtansine, a microtubule inhibitor, as its cytotoxic payload.
• T-DXd (fam-trastuzumab deruxtecan): Utilizes deruxtecan, a topoisomerase I inhibitor, which allows it to be effective even in tumors with lower HER2 expression.

Clinical Applications

• Adjuvant Strategy: T-DM1 is the established standard for HER2+ early breast cancer patients who have residual invasive disease at the time of surgery after neoadjuvant therapy.
• Metastatic Strategy: T-DXd is now the preferred second-line option for HER2+ metastatic disease, having demonstrated superior progression-free and overall survival compared to T-DM1 in the DESTINY-Breast03 trial.
• HER2-Low Disease: T-DXd is uniquely approved for HER2-low metastatic breast cancer (IHC 1+ or IHC 2+/ISH-negative), a category for which T-DM1 is not indicated.

Safety and Dosing

• Specific Toxicities: T-DM1 is more commonly associated with thrombocytopenia, peripheral neuropathy, and elevated liver enzymes. T-DXd carries a significant black box warning for interstitial lung disease (ILD) and pneumonitis, which can be fatal and requires vigilant monitoring.
• Dosing Schedules: While both are given every 21 days, the standard doses differ: 3.6 mg/kg for T-DM1 and 5.4 mg/kg for T-DXd.

Q10. A patient with ER+/HER2+ metastatic breast cancer progresses after trastuzumab + pertuzumab + taxane. What is the next best option?

For a patient with ER+/HER2+ metastatic breast cancer who progresses after first-line trastuzumab, pertuzumab, and a taxane, the current preferred second-line option is fam-trastuzumab deruxtecan (T-DXd).

Rationale and Evidence

• Superiority: This recommendation is based on the DESTINY-Breast03 trial, which demonstrated significant improvements in both progression-free survival (PFS) and overall survival (OS) compared to the historical standard, ado-trastuzumab emtansine (T-DM1).
• ER+ Integration: Because the patient is hormone receptor-positive, guidelines allow for the addition of endocrine therapy (such as an aromatase inhibitor or fulvestrant) to the HER2-targeted therapy once cytotoxic chemotherapy is discontinued.
• Alternative Option: If a patient is not a candidate for T-DXd, ado-trastuzumab emtansine (T-DM1) remains a recommended second-line alternative.

Dynamic Treatment Sequencing

If the patient's recurrence had occurred within 12 months of finishing adjuvant trastuzumab-based therapy, clinicians are advised to move directly to these second-line recommendations rather than repeating first-line regimens.

Correct Answers:

1. D. Docetaxel and cyclophosphamide (TC) followed by tamoxifen (for RS = 26)
2. A. Anastrozole x 5 years
3. A. Anastrozole (RS = 11)
4. C. Tamoxifen x 10 years
5. B. Anastrozole + abemaciclib
6. D. Olaparib
7. D. Capecitabine
8. C. TCH + pertuzumab x 6 cycles
9. A. Every 12 weeks
10. B. Ado-trastuzumab emtansine (with residual disease)
11. C. Trastuzumab + pertuzumab (without risdual disease)
12. Hold trastuzumab and pertuzumab
13. B. Pembrolizumab + carboplatin + paclitaxel → pembrolizumab + doxorubicin + cyclophosphamide (AC)
14. C. Dose dense doxorubicin + cyclophosphamide (AC) → paclitaxel
15. B. Fam-trastuzumab deruxtecan
16. D. Trastuzumab + pertuzumab + docetaxel
17. B. Ado-trastuzumab emtansine
18. A. Ribociclib + letrozole
19. D. Elacestrant
20. B. Talazoparib
21. A. Initiate denosumab every 6 months
22. B. Embryo cryopreservation
23. C. Zoledronic acid 4 mg IV every 12 weeks
24. D. Discontinue tamoxifen; start goserelin and anastrozole
25. D. Abemaciclib + letrozole + goserelin
26. A. Palbociclib + letrozole
27. C. Alpelisib + fulvestrant + goserelin
28. B. Everolimus + exemestane
29. D. Abemaciclib + anastrozole
30. B. Everolimus + exemestane
31. A. Alpelisib and fulvestrant
32. Correct Answer: C – “You should start CBE, mammogram when you are 39 years old then yearly”
33. A. Ixabepilone

TS is a 36-year-old premenopausal white female who presents with a diagnosis of lobular carcinoma in situ (LCIS). She has a significant family history of breast cancer, including her mother, maternal grandmother, and maternal aunt who were all diagnosed prior to 60 years of age. TS had one child at age 31 and no history of oral contraceptive use or estrogen replacement therapy. She was 12 years old at first menarche. What are TS’s risk factors for the development of invasive ductal carcinoma?

• A. Premenopausal status, family history, race, and LCIS
• B. LCIS, family history, early age of menarche, age > 30 at birth of first child
• C. Family history, race, early age of menarche, age > 30 at birth of first child
• D. Premenopausal status, age, LCIS, and < 3 pregnancies

The correct answer is B.
TS is at an increased risk for developing invasive breast cancer due to her LCIS, significant family history, early age of menarche, and age > 30 at birth of her first child.

• Answer A is incorrect because premenopausal status and race are not risk factors.
• Answer C is incorrect because race is not a risk factor.
• Answer D is incorrect because her age, premenopausal status, and number of pregnancies (other than nulliparity) are not risk factors.

Correct answer is A.

TS’s >20% lifetime risk of breast cancer and diagnosis of LCIS put her at a high-risk for development of breast cancer. Risk reduction strategies for TS include bilateral total mastectomy, bilateral salpingo-oophorectomy or chemoprevention with tamoxifen given that she is ≥ age 35. Salpingo-oophorectomy is an option if BRCA 1/2 mutation is strongly suspected.

• Answer B is incorrect because luteinizing hormone-releasing hormone (LHRH agonists) (including goserelin) are not appropriate as a risk reduction strategy.
• Answer C is incorrect because aromatase inhibitors are only indicated in postmenopausal women.
• Answer D is incorrect because raloxifene is only indicated in postmenopausal women.

If TS were postmenopausal her options for risk reduction would include bilateral total mastectomy, or chemoprevention with tamoxifen, raloxifene, or an aromatase inhibitor.

TS should receive screening according to high-risk guidelines. NCCN screening recommendation for TS include CBE every 6 – 12 months, annual mammography, and annual breast MRI. ACS recommends annual mammography and breast MRI.

CW is a postmenopausal female with a new diagnosis of ER-positive, PR-positive, HER2-negative breast cancer. Her disease is clinically staged as T2 N2 M0 (with a 3 cm primary tumor and 4 positive LNs). She was treated with neoadjuvant chemotherapy followed by breast conserving surgery and radiation. CW has no major comorbidities and desires to be aggressive with treatment.

What is the most appropriate adjuvant endocrine therapy for CW?

• A. Anastrozole + leuprolide
• B. Anastrozole + abemaciclib
• C. Anastrozole
• D. Tamoxifen

Correct answer is B.

ASCO and NCCN Guidelines recommend the addition of abemaciclib for 2 years to endocrine therapy for patients at a high risk for recurrence. Criteria for high-risk of recurrence includes patients with ≥ 4 positive LN or 1 – 3 positive LN with at least one additional high-risk feature. Given that CW has 4 positive lymph nodes, she meets this high-risk criterion. This recommendation is based on the results of the MonarchE trial in which the addition of abemaciclib to endocrine therapy improved iDFS compared to endocrine therapy alone.

• Answer A is incorrect because leuprolide is only indicated for premenopausal patients. CW is postmenopausal and therefore, does not need the addition of leuprolide.
• Answer C is incorrect because this patient meets high-risk criteria established for the addition of abemaciclib and the patient desires to be aggressive with treatment. If she does not tolerant or declines the addition of abemaciclib, single agent AI (such as anastrozole) would be an appropriate adjuvant treatment option.
• Answer D is incorrect because tamoxifen is only recommended for patients who are unable to tolerate an aromatase inhibitor, which is the preferred endocrine therapy for postmenopausal patients, such as CW.

HF is a 60-year-old healthy female with minimal comorbidities, including hyperlipidemia and hyperthyroidism. She has a newly diagnosed Stage IIIB (T4, N2, M0) left breast cancer that is ER 70%, PR 0%, and HER2 IHC 3+. She would prefer a lumpectomy and radiation; therefore, she must undergo neoadjuvant chemotherapy with the hope of decreasing the size of the primary tumor to allow for adequate surgical resection.

What neoadjuvant regimen would be most appropriate?

• A. AC + trastuzumab x 4 cycles
• B. Docetaxel + trastuzumab + pertuzumab x 6 cycles
• C. TCH + pertuzumab x 6 cycles
• D. AC x 4 cycles → paclitaxel weekly x 12

Answer C is correct.

It is preferred that HF receives a neoadjuvant chemotherapy regimen with or without pertuzumab. Any regimen listed in table “Selected Neoadjuvant/Adjuvant Therapy for HER2-positive Breast Cancer” would be appropriate according to NCCN Guidelines®. Based on the results of the TRYPHAENA study, HF will receive docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) x 6 cycles.

• Answer A is incorrect because trastuzumab should not be given concurrently with an anthracycline-containing regimen due to the increased risk for cardiotoxicity.
• Answer B is incorrect because docetaxel + trastuzumab + pertuzumab is recommended for metastatic breast cancer not as neoadjuvant therapy.
• Answer D is incorrect because HF should receive a neoadjuvant regimen that contains HER2-directed therapy.

HF is planned to receive docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) x 6 cycles followed by surgery for her diagnosis of HER2-positive, stage IIIB breast cancer. According to pertuzumab’s prescribing information, what is an appropriate frequency for monitoring HF’s LVEF during neoadjuvant therapy following baseline assessment?

• A. Every 12 weeks
• B. Every 6 months
• C. Every 6 weeks
• D. Every 2 months

The correct answer is A.

Monitoring of LVEF with an ECHO or MUGA is recommended by pertuzumab’s prescribing information at baseline and every 12 weeks during neoadjuvant treatment (at least once during neoadjuvant therapy).

The correct answer is B.

It is recommended to hold trastuzumab and pertuzumab if the LVEF is < 50% with a fall of ≥ 10% points below pre-treatment value in patients receiving neoadjuvant or adjuvant treatment with trastuzumab and pertuzumab. This patient had an absolute decrease in 15% and an LVEF < 50%.

Answer A, C, and D, are incorrect because this patient meets the criteria above to hold trastuzumab and pertuzumab.

BZ is a 50-year-old postmenopausal woman who presents with jaundice, dyspnea on exertion, and fatigue. Workup reveals a left breast cancer that has metastasized to the liver and lung, which is the cause of her symptoms. The pathology is ER=0%, PR=0%, HER2-negative, PD-L1 negative, and germline BRCA1/2 positive. Which of the following first-line regimens is the most appropriate for BZ at this time?

• A. Rucaparib
• B. Talazoparib
• C. Gemcitabine
• D. Docetaxel

Correct answer is B. Talazoparib.

The EMBRACA trial, which compared talazoparib with physician’s choice of chemotherapy for patients with germline BRCA1/2 mutation, found an improved median PFS and response rate in the talazoparib group. As a result, olaparib or talazoparib are preferred treatment options for patients with germline BRCA1/2 mutations in the NCCN Guidelines.

• Answer A is incorrect because the PARP inhibitor rucaparib has not been adequately studied for use in breast cancer at this time.
• Answer C and D are incorrect because the PARP inhibitors olaparib and talazoparib have shown an improved median PFS and response rate compared to chemotherapy. Chemotherapy, such as gemcitabine or docetaxel, could be considered for this patient as second-line therapy after a PARP inhibitor.

AH is a 50-year-old postmenopausal female who is receiving adjuvant treatment with letrozole x 5 years for the treatment of an ER-positive, PR-positive, HER2-negative stage IA breast cancer. Her baseline dual-energy X-ray absorptiometry (DXA) scan reveals a T-score of -2.7. She is taking calcium 1,500 mg PO divided twice daily and vitamin D3 800 international units PO daily. In addition to encouraging physical activity and continued calcium and vitamin D supplementation, which of the following is the most appropriate action based on her DXA scan?

• A. Initiate denosumab every 6 months
• B. Observation
• C. Increase calcium and vitamin D supplementation
• D. Initiate zoledronic acid every 4 weeks

The correct answer is A.

Initiate denosumab every 6 months. Given that AH has osteoporosis at baseline and is taking an AI (letrozole) which is well-known to cause bone loss, NCCN task force and guidelines recommend initiating a bone modifying agent. Other acceptable options include zoledronic acid 4 mg every 6 months or zoledronic acid (Reclast) 5 mg every year. Oral bisphosphonates could also be considered for this patient. A DXA scan should be repeated every 2 years.

• Answer B is incorrect because the patient is a candidate for a bone modifying agent (for reasons listed above).
• Answer C is incorrect because AH is already taking appropriate amounts of supplemental calcium and vitamin D.
• Answer D is incorrect because zoledronic acid is typically dosed every 6 months or annually for treatment of bone loss

YC is a 37-year-old premenopausal female who was diagnosed with triple negative stage IA breast cancer. She had a modified radical mastectomy and is planned to receive adjuvant treatment in 3 weeks with dose dense doxorubicin + cyclophosphamide (AC) x 4 cycles followed by weekly paclitaxel. She is interested in fertility preservation options.

Based on the ASCO guideline on fertility preservation, which option is most appropriate for YC at this time?

• A. Ovarian transposition
• B. Embryo cryopreservation
• C. Ovarian tissue cryopreservation
• D. Leuprolide

The correct answer is B.

YC should be referred to a fertility specialist as soon as possible (prior to the initiation of chemotherapy). According to the ASCO guideline, embryo cryopreservation and cryopreservation of unfertilized oocytes are considered viable options for this patient. Based on the results of the POEMS trial, the use of LHRH agonists, such as goserelin 3.6 mg SQ monthly starting 1 week prior to chemotherapy and continuing until the completion of chemotherapy, is an option for this patient; however, the ASCO guideline considers the use of LHRH agonists to be investigational

• Answer A is incorrect because ovarian transposition would only be recommended for patients undergoing irradiation as part of their cancer treatment.
• Answer C is not the most appropriate option because ovarian tissue cryopreservation is considered an investigational procedure at this time and therefore, should not be routinely recommended.
• Answer D is not the most appropriate answer because LHRH agonists are considered an investigational option according to the ASCO guidelines. Based on the recent results of the POEMS and PROMISE-GIM6 studies, this option could be considered in select patients; however, this is not currently supported by the ASCO or ASRM guidelines.

FR is a 37-year-old premenopausal woman who is receiving endocrine therapy for newly diagnosed bone metastases. Since FR has metastatic breast cancer to the bone, the addition of a supportive therapy for bone metastasis would also be discussed with the patient. Her CrCl is within normal limits.

According to ASCO and NCCN Guidelines®, which of the following is the most appropriate regimen to prevent skeletal-related events (SREs)?

• A. Denosumab 60 mg SQ every 6 months
• B. Pamidronate 90 mg IV every 6 months
• C. Zoledronic acid 4 mg IV every 12 weeks
• D. Denosumab 120 mg SQ every 12 weeks

The correct answer is C.

Zoledronic acid 4 mg IV every 12 weeks.

• Answer A is incorrect because denosumab 60 mg SQ every 6 months is indicated for osteopenia and osteoporosis and would not be appropriate for a patient with bone metastases.
• Answer B is incorrect because pamidronate should be given every 3 – 4 weeks.
• Answer D is incorrect because denosumab should be given every 4 weeks.

Baseline renal function should be evaluated for all BMAs and prior to each dose of bisphosphonates. Serum calcium, electrolytes, phosphate, magnesium, and hematocrit/hemoglobin should be monitored regularly with bisphosphonates. She would continue on a BMA for at least 2 years, or until there is a significant deterioration in her performance status.

FR is a 37-year-old premenopausal woman with a history of breast cancer. She was originally diagnosed four years ago with stage IIB (T2, N1, M0), ER/PR-positive, HER2-negative invasive ductal carcinoma. She underwent a modified radical mastectomy and adjuvant chemotherapy with dose dense AC followed by weekly paclitaxel. After completing chemotherapy, she initiated tamoxifen with a planned initial duration of 5 years. Now 2 years after starting tamoxifen, she presents to her oncologist with severe back pain x 3 weeks. A bone scan reveals multiple areas of increased uptake in her thoracic and lumbar spine. Biopsy of T3 confirms metastatic breast cancer that is now ER+, PR+, and HER2-positive (IHC 3+). CT of the chest/abdomen was negative for other sites of metastases.

FR has bone-only metastases; her disease is now ER/PR positive, HER2-positive, and she is relatively asymptomatic (pain controlled with OTC analgesics). Given that she experienced disease progression while receiving endocrine therapy and there is a known survival benefit for chemotherapy + HER2-targeted therapy, her oncologist treated her with docetaxel, trastuzumab, and pertuzumab (THP) x 6 cycles with a good response. She is now planned to continue maintenance trastuzumab and pertuzumab and restart endocrine therapy. FR’s estradiol and FSH levels are still in the premenopausal range.

What is the most appropriate endocrine treatment for FR’s metastatic disease?

• A. Continue tamoxifen
• B. Discontinue tamoxifen; start exemestane
• C. Continue tamoxifen; add fulvestrant
• D. Discontinue tamoxifen; start goserelin and anastrozole

Correct answer is D.

Given that FR’s breast cancer recurred while receiving tamoxifen and she is premenopausal, it would be appropriate to discontinue tamoxifen and initiate 2nd-line therapy with OAS and endocrine therapy as for postmenopausal women. FR will receive ovarian suppression with goserelin in combination with anastrozole. She should continue to receive endocrine therapies sequentially at time of disease progression unless her disease becomes endocrine-refractory, she progresses through endocrine options, or she develops symptomatic metastatic disease at which time chemotherapy would be indicated.

FR is also prescribed trastuzumab every 3 weeks since her disease now HER2-positive.

• Answer A is incorrect because endocrine therapy should be modified since her disease has recurred on tamoxifen.
• Answer B is incorrect because she is premenopausal; therefore, she should be treated with an LHRH agonist in addition to an AI.
• Answer C is incorrect because the combination of fulvestrant and tamoxifen is not recommended by ASCO or NCCN Guidelines.

HZ is a 47-year-old postmenopausal female who was diagnosed with ER-positive, PR-negative, HER2-negative stage 1A invasive ductal carcinoma 2 years ago. She was treated with a breast-conserving surgery followed by radiation and anastrozole. She presents to her medical oncologist for follow-up after 18 months of receiving anastrozole. She is noted to have new onset back and hip pain, which is due to metastatic breast cancer to the bone. The pathology of the metastatic site is also ER-positive, PR-negative, and HER2-negative. The tissue sample of the metastatic lesion is also found to be PIK3CA-mutated and BRCA-negative.

What is the most appropriate option to treat HZ’s metastatic breast cancer?

• A. Alpelisib and fulvestrant
• B. Everolimus
• C. Doxorubicin and cyclophosphamide (AC)
• D. Olaparib

Correct answer is A.

Alpelisib is a PIK3CA inhibitor that is indicated in combination with fulvestrant for postmenopausal women with HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer that have progression on or after an endocrine-based regimen. HZ meets this criteria since she had progression while receiving adjuvant anastrozole. NCCN Guidelines® consider alpelisib and fulvestrant a category 1 regimen for patients with PIK3CA-mutated advanced or metastatic breast cancer.

• Answer B is incorrect because everolimus as a single-agent is not indicated for the treatment of metastatic breast cancer.
• Answer C is incorrect because chemotherapy could be considered in this patient at some point in her treatment; however, alpeslib and fulvestrant is a more appropriate option given her PIK3CA-mutated disease and lack of visceral crisis.
• Answer D is incorrect because olaparib is only an appropriate option for patients with recurrent or metastatic HER2-negative, BRCA1/2-positive breast cancer. HZ has BRCA-negative breast cancer.

A 21-year-old female, her mother was diagnosed of breast cancer at 49 years old. She asks you about your recommendation for her to start breast cancer screening.

• A. You should start CBE, mammography as soon as possible then yearly
• B. You should start CBE, mammography & MRI as soon as possible then yearly
• C. You should start CBE, mammography when you are 39 years old then yearly
• D. You should start CBE, mammography & MRI when you are 39 years old then yearly

Answer & Explanation

Correct Answer: C – “You should start CBE, mammogram when you are 39 years old then yearly”

Reasoning:

• General guidance (NCCN/ACS/USPSTF): Women with a first-degree relative with breast cancer should begin screening 10 years earlier than the age of diagnosis of the youngest affected relative, but not before age 30 for mammography.
• In this case: Mother diagnosed at 49 → daughter should start at 39.
• At 21, no mammography or MRI is recommended unless she has a known BRCA mutation or very high-risk genetic predisposition.
• Clinical breast exam (CBE) and breast self-awareness can be encouraged earlier, but imaging (mammography/MRI) waits until the appropriate age/risk threshold.

If she had BRCA mutation or high genetic risk, MRI screening would start at age 25–30, but with only one FDR (mother at 49), the guideline is 39 years old.

KL is a 56-year-old patient diagnosed with Stage IIB breast cancer 7 months ago. Her ER=30%, PR=11%, and HER2 neu IHC +1. She had a lumpectomy, then 4 cycles of EC, followed by 6 cycles of weekly paclitaxel. Recently, she felt severe pain in her upper quadrant, and a CT scan confirmed metastatic disease to the liver. A biopsy confirmed the same molecular subtype as her breast mass. Which of the following would you recommend as treatment for her metastatic disease?

• A. Ixabepilone
• B. Continue paclitaxel and add gemcitabine
• C. Carboplatin single agent
• D. Continue paclitaxel and add Eribulin

Answer:

• Patient profile: 56-year-old female with metastatic breast cancer (MBC) to the liver.
• Tumor subtype: ER 30%, PR 11%, HER2 IHC 1+ → Hormone receptor-positive (HR+) / HER2-negative.
• Prior treatment:
  • Surgery: Lumpectomy
  • Chemotherapy: 4 cycles EC (epirubicin + cyclophosphamide) → 6 cycles weekly paclitaxel
• Current issue: Metastatic disease confirmed on liver biopsy, same molecular subtype.

Key points for treatment decision:

1. She already received adjuvant anthracycline (EC) and taxane (paclitaxel).
2. The disease progressed shortly after completing taxane therapy, so this is taxane-resistant metastatic disease.
3. Tumor is HR+/HER2-, so endocrine therapy ± CDK4/6 inhibitor would normally be first-line for metastatic HR+/HER2- disease. However, rapid progression to liver metastases with symptomatic disease often warrants chemotherapy rather than endocrine therapy initially.

Option analysis:

• A. Ixabepilone – A microtubule inhibitor approved for metastatic breast cancer resistant to anthracyclines and taxanes. Could be considered.
• B. Continue paclitaxel + gemcitabine – Not recommended because she is progressing on paclitaxel; continuing the same drug is unlikely to help.
• C. Carboplatin single agent – Platinum monotherapy is less effective in HR+/HER2- disease; mainly used for triple-negative or BRCA-mutated tumors.
• D. Continue paclitaxel + Eribulin – Again, continuing paclitaxel does not make sense; Eribulin can be used as single-agent later.

Best choice: A. Ixabepilone – appropriate for taxane-resistant metastatic breast cancer.

Summary: KL has taxane-resistant metastatic HR+/HER2- breast cancer, and Ixabepilone is indicated in this setting. Continuing paclitaxel is not effective. Carboplatin is not first-line in HR+/HER2-, and Eribulin is generally used after anthracycline and taxane failure, but as a single agent, not combined with a failed taxane

Exam Tricks & “Gotchas”

• Adjuvant therapy duration: Trastuzumab is 1 year total, not indefinite.
• Switch to T-DM1 if residual HER2+ disease after neoadjuvant.
• Endocrine therapy sequencing: Tamoxifen (premenopausal) → AI (postmenopausal).
• Avoid SSRIs that block CYP2D6 in tamoxifen users.
• AI therapy → monitor bone health & consider bisphosphonate.
• HER2 therapies all require LVEF monitoring (trastuzumab, pertuzumab, T-DM1, trastuzumab deruxtecan).
• TNBC → immunotherapy only if PD-L1 positive.

1. P.S. is a 69-year-old woman with a history of New York Heart Association class II heart failure, coronary artery disease, and hypertension. She was recently given a diagnosis of T2N1M0 breast cancer. Additional diagnostic tests reveal that her tumor is hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) negative. In addition to mastectomy and radiation, which one of the following is the best chemotherapy option for P.S. at this time?

• (A) Doxorubicin and cyclophosphamide (AC) for four cycles, followed by paclitaxel for four cycles.
• (B) Cyclophosphamide, methotrexate, and fluorouracil (CMF) for six cycles.
• (C) Docetaxel, doxorubicin, and cyclophosphamide (TAC) for six cycles.
• (D) Docetaxel plus cyclophosphamide (TC) for four cycles.

2. J.W. is a 64-year-old woman recently given a diagnosis of stage IIA breast cancer. She has a medical history significant for type 2 diabetes mellitus, deep vein thrombosis, and osteopenia (T-score of —1). Which one of the following is the best endocrine option for J.W.?

• (A) Tamoxifen for 5 years.
• (B) Tamoxifen for 2 years, followed by letrozole for an additional 3 years.
• (C) Anastrozole for 5 years.
• (D) Goserelin for 2 years, followed by anastrozole for 3 years.

3. Questions 3 and 4 pertain to the following case. T.T. is a 56-year-old perimenopausal woman with a medical history significant for appendectomy, received a diagnosis of T3N2M0 breast cancer. Additional prognostic tests reveal that her tumor is HR positive, poorly differentiated, and negative for HER2 overexpression. In addition to mastectomy and radiation, which one of the following systemic treatment approaches is best for T.T. at this time?

• (A) AC for four cycles, followed by paclitaxel for four cycles.
• (B) Cyclophosphamide, epirubicin, and fluorouracil for six cycles.
• (C) TC for four cycles.
• (D) CMF for six cycles.

4. T.T. elects to receive adjuvant endocrine therapy. Which one of the following endocrine agent regimens is the best option for her at this time?

• (A) Letrozole for 5 years, followed by tamoxifen for 5 years.
• (B) Letrozole for 3 years, followed by tamoxifen for 2 years.
• (C) Tamoxifen for 2 years, followed by anastrozole for 3 years.
• (D) Tamoxifen for 5 years, followed by anastrozole for 5 years.

5. P.M. is a 51-year-old woman who recently was given a diagnosis of breast cancer. Examination of her cancer reveals that her tumor is 1 cm in size, lymph node (LN) negative, HR negative, poorly differentiated (grade 3 differentiation), and positive for HER2 overexpression. P.M.’s medical history is not significant; however, she has a strong family history significant for colon cancer, lung cancer, and breast cancer in her paternal grandmother. Which one of the following factors should have the greatest consideration when determining P.M.’s need for adjuvant therapy?

• (A) Stage of breast cancer.
• (B) Histologic tumor characteristics.
• (C) Family history of cancer.
• (D) Age.

6. J.T. is a 53-year-old postmenopausal woman given a diagnosis of T1N1M0 breast cancer. She will begin therapy with conventional AC, followed by paclitaxel. This will be followed by 5 years of tamoxifen therapy. A newly graduated nurse will infuse her chemotherapy today. Which one of the following concepts is best for the nurse to be educated about?

• (A) Growth factor support to prevent febrile neutropenia.
• (B) Bisphosphonate therapy to prevent endocrine-related bone loss.
• (C) Aprepitant to prevent chemotherapy- induced nausea and vomiting.
• (D) Gabapentin therapy to prevent peripheral neuropathy.

7. K.W. is a healthy 49-year-old woman with no significant medical history. She is given a diagnosis of a T4N1M0, HR-positive, HER2-positive, well-differentiated (grade 1) breast cancer. In addition to trastuzumab and radiation, which one of the following is the best treatment option for K.W.?

• (A) Surgery, followed by chemotherapy; then endocrine therapy for 5 years.
• (B) Endocrine therapy for 4 months, followed by surgery; then endocrine therapy to complete 5 years of total endocrine therapy.
• (C) Chemotherapy, followed by surgery; then endocrine therapy for 5 years.
• (D) Endocrine therapy for 4 months, followed by surgery; then chemotherapy.

8. J.S. is a 65-year-old woman with T1N0M0 breast cancer. She has a medical history significant for hypertension, chronic obstructive pulmonary disease, osteopenia (bone mineral density T-score of —1), and protein S deficiency. She was recently treated with mastectomy, followed by radiation and chemotherapy with CMF for six cycles. J.S. will now receive adjuvant endocrine therapy. Knowing J.S.’s history of osteopenia, the physician wants to prevent additional bone loss. Which one of the following is the best approach for J.S.?

• (A) Anastrozole 1 mg/day plus calcium and vitamin D supplementation.
• (B) Tamoxifen 10 mg/day plus calcium and vitamin D supplementation.
• (C) Tamoxifen 10 mg/day plus zoledronic acid 4 mg intravenously every 6 months.
• (D) Letrozole 2.5 mg/day plus zoledronic acid 4 mg intravenously every 6 months.

9. L.Z. is a 55-year-old woman with recently diagnosed T3N1M0 early breast cancer (EBC). Her breast cancer is moderately differentiated (grade 2), HR positive, and negative for HER2 overexpression. She has a family history significant for breast cancer in her maternal aunt, who received the diagnosis at age 60, and breast cancer in her paternal grandmother, diagnosed at age 69. Which one of the following factors is most associated with a poor prognosis in L.Z.?

• (A) Stage of her breast cancer.
• (B) Histologic characteristics of her primary tumor.
• (C) Her family history of breast cancer.
• (D) Her age.

10. A.S., a 69-year-old woman with diabetes mellitus, hypertension, and chronic obstructive pulmonary disease, has a diagnosis of T4N0M0 breast cancer. Analysis of her tumor reveals that it is moderately differentiated (grade 2), ER and progesterone receptor positive, and HER2 negative. In addition to radiation therapy, which one of the following is the best approach to manage her cancer at this time?

• (A) Endocrine therapy for 3 months, followed by surgery and chemotherapy for four to six cycles.
• (B) Chemotherapy for four to six cycles, followed by surgery and endocrine therapy for 5 years.
• (C) Endocrine therapy for 3 months, followed by surgery and endocrine therapy to complete 5 years of therapy.
• (D) Surgery, followed by endocrine therapy for 5 years.

11. D.J. is a 58-year-old perimenopausal woman with early-stage breast cancer. Her primary tumor is 0.5 cm, and her LNs are pathologically negative according to her sentinel LN biopsy. Her breast cancer is well differentiated (grade 1), positive for ERs, and negative for progesterone receptors and HER2. In addition to lumpectomy and radiation, which one of the following adjuvant regimens is best for D.J. at this time?

• (A) CMF for six cycles, followed by anastrozole for 5 years.
• (B) Tamoxifen for 5 years, followed by letrozole for 5 years.
• (C) Fluorouracil, doxorubicin, and cyclophosphamide for four cycles, followed by tamoxifen for 5 years.
• (D) Anastrozole for 5 years.

12. P.C. is a 69-year-old postmenopausal woman with stage IIB breast cancer and a medical history significant for hypertension, diabetes mellitus, fibromyalgia, and rheumatoid arthritis. She has undergone mastectomy and systemic adjuvant chemotherapy; she will begin adjuvant endocrine therapy. She is concerned about some of the adverse effects associated with hormone therapy and the ways in which they will affect her current medical conditions and associated symptoms. Given her medical history and concerns, which one of the following is the best therapeutic option for P.C. at this time?

• (A) Anastrozole 1 mg/day orally.
• (B) Goserelin 3.6 mg subcutaneously every 28 days.
• (C) Tamoxifen 20 mg/day orally.
• (D) Letrozole 2.5 mg/day orally.

13. T.D., a 59-year-old postmenopausal woman, comes to the clinic with complaints of a painless, nonmobile lump in her right breast. Her examination reveals a 3-cm invasive ductal carcinoma. Pathologic tests show that it is negative for HRs but positive for HER2 and LN involvement. T.D. has a medical history significant for diabetes mellitus, hypertension, and Hodgkin’s lymphoma, which was treated with mediastinal radiation therapy. T.D. and her oncologist discuss potential treatment options. During this discussion, T.D. reveals that she would like to conserve breast tissue if possible. In addition to trastuzumab therapy, which one of the following approaches is best for T.D.?

• (A) CMF for six cycles, followed by lumpectomy.
• (B) Mastectomy, followed by dose- dense AC for four cycles; then paclitaxel for four cycles.
• (C) Fluorouracil, doxorubicin, and cyclophosphamide for six cycles, followed by lumpectomy.
• (D) Mastectomy, followed by TC for four cycles.

14. A.J.B. is a 70-year-old postmenopausal woman who has been receiving tamoxifen 20 mg/day for the past 4 months for her stage IIB, HR-positive, HER2-negative breast cancer. She has been admitted to the hospital with complaints of shortness of breath, chest pain, and dizziness. She is given a diagnosis of pulmonary embolism and concomitant right lower extremity deep vein thrombosis. She is initiated on intravenous unfractionated heparin and warfarin therapy. Which one of the following approaches is best for A.J.B.’s breast cancer therapy?

• (A) Discontinue tamoxifen and begin exemestane 25 mg/day orally.
• (B) Decrease tamoxifen to 10 mg/day orally and increase the target international normalized ratio to 3.5.
• (C) Discontinue tamoxifen and begin anastrozole 1 mg/day orally.
• (D) Continue tamoxifen 20 mg/day but increase the target international normalized ratio to 3.5.

15. M.R., a 68-year-old woman, undergoes mammography, ultrasound examination, and core needle biopsy of the breast. Results reveal a T1N1M0 breast cancer. She was initially treated with a mastectomy, radiation, and chemotherapy with AC for four cycles. She has received adjuvant endocrine therapy with anastrozole 1 mg/day orally for the past 2 months. Today, she presents to the clinic with complaints of occasional mild hot flashes. Which one of the following is the best approach to M.R.’s complaints?

• (A) Discontinue anastrozole and begin letrozole 2.5 mg/day orally.
• (B) Discontinue anastrozole and begin tamoxifen 20 mg/day orally.
• (C) Maintain anastrozole and start clonidine 0.1 mg/day orally.
• (D) Maintain anastrozole and add venlafaxine extended release 37.5 mg/day orally.

16. H.C. is a 45-year-old woman with a medical history significant for hypertension, psoriasis, and hypercholesterolemia. Her family history is significant for breast cancer in her mother, diagnosed at age 69; and breast cancer in her paternal aunt, diagnosed at age 59. H.C. was given a diagnosis of T1N1M0 breast cancer 4 years ago. She was treated with mastectomy and radiation and was then initiated on tamoxifen 20 mg/day orally. She comes to the clinic today with complaints of bloody vaginal discharge. Which one of the following causes the most concern regarding H.C.’s vaginal discharge?

• (A) Tamoxifen.
• (B) Perimenopause.
• (C) Infection.
• (D) Endometrial cancer.

17. P.N. is a 67-year-old postmenopausal woman with a medical history significant for congestive heart failure, diabetes mellitus, and arthritis. Her diagnosis is T2N1M0 breast cancer. Analysis of her tumor reveals that it is ER, progesterone receptor, and HER2 positive. In addition to surgery, radiation, and endocrine therapy, which one of the following is the most appropriate adjuvant systemic option for P.N. at this time?

• (A) Fluorouracil, doxorubicin, and cyclophosphamide for six cycles followed by trastuzumab therapy.
• (B) TAC for four cycles with concurrent trastuzumab therapy.
• (C) CMF for six cycles followed by trastuzumab therapy.
• (D) Docetaxel and carboplatin with concurrent trastuzumab therapy.

18. S.R. is a 62-year-old woman with a medical history significant for depression, gastroesophageal reflux disease, diabetes mellitus, coronary artery bypass graft, gastrointestinal bleeding, and, most recently, T2N1M0 breast cancer. Her medication history consists of ranitidine, insulin, and calcium and vitamin D supplementation. She recently completed dose-dense chemotherapy with AC and began sequential paclitaxel therapy. She returns to the clinic today after two doses of paclitaxel with complaints of painful numbness and tingling in her hands and feet. Which one of the following is the best approach to manage S.R.’s symptoms?

• (A) Ibuprofen 600 mg orally three times daily.
• (B) Transdermal fentanyl 25-mcg patch placed every 3 days.
• (C) Oxycodone 5 mg orally every 4 hours as needed for pain.
• (D) Acetaminophen 500 mg orally twice daily.

19. C.O., an 82-year-old woman, was recently given a diagnosis of breast cancer. Mammography, core needle biopsy, axillary LN staging, and pathologic analysis of her cancer reveal that she has a T1N0M0 breast cancer that is HR positive, HER2 negative, and well differentiated. C.O. also has a history of hypertension, congestive heart failure, pulmonary embolism, and depression. Her performance status is relatively poor; however, she seeks treatment of her breast cancer. Which one of the following is the best primary treatment option for C.O. at this time?

• (A) Mastectomy, followed by radiation; then AC for four cycles, followed by paclitaxel for four cycles and anastrozole for 5 years.
• (B) Tamoxifen for 4 months, followed by lumpectomy and radiation.
• (C) Mastectomy, followed by radiation and CMF six cycles; then tamoxifen for 5 years.
• (D) Mastectomy, followed by radiation and anastrozole for 5 years.

20. B.S. is a 57-year-old woman given a diagnosis of T1N1M0 breast cancer about 2 years ago. She was treated with lumpectomy, radiation therapy, and chemotherapy. Since then, she has been taking tamoxifen 20 mg/day orally. B.S. informs the pharmacist that she currently takes gemfibrozil for hypercholesterolemia, atenolol for hypertension, topical emollients for vaginal dryness, calcium and vitamin D supplementation to maintain bone mass, and, recently, paroxetine for “mood.” Which one of the following concerns is most important for the pharmacist to discuss with the oncologist?

• (A) Menopausal status.
• (B) Treatment of her mood.
• (C) Vaginal symptoms.
• (D) Bone mineral density.

21. Questions 21 and 22 pertain to the following case. J.J., a 65-year-old African American woman, presented to the outpatient clinic after her first- ever mammogram and subsequent breast biopsy. Before her examination, the patient admitted to having had pain in her right breast for about 1 year but had not gone for an evaluation. In addition, J.J. complains of right abdominal pain for about 2 months, not relieved with around-the- clock hydrocodone therapy. This pain keeps her awake at night, and she is unable to complete activities of daily living. Breast biopsy revealed invasive ductal carcinoma that is estrogen receptor (ER) negative, progesterone receptor (PR) 2%, and human epidermal growth factor receptor 2 (HER2) negative. Her computed tomography (CT) scan of the abdomen revealed two liver lesions (0.7 cm and 1.1 cm) consistent with metastatic disease. J.J.’s medical history is significant for obesity, hyperlipidemia, hypertension, and diabetes mellitus. Which one of the following is the best treatment
for J.J. at this time?

(A) Hormonal therapy.
(B) Single-agent chemotherapy.
(C) Combined chemotherapy and biologic therapy.
(D) Combination chemotherapy.

22. J.J. responds well to treatment and is able to perform activities of daily living. In the past 2 weeks, however, she has noticed increased pain in her left arm that never goes away; she does not remember falling or experiencing any trauma to the area. A radiograph reveals a suspicious lesion in her left arm. A bone scan demonstrates increased uptake in the left humerus and right femur consistent with metastatic disease. Which one of the following is the best therapeutic option for J.J. at this time?

• (A) Zoledronic acid 4 mg intravenously monthly.
• (B) Pamidronate 90 mg intravenously monthly.
• (C) Alendronate 70 mg orally once daily.
• (D) Risedronate 35 mg orally once weekly.

23. Questions 23 and 24 pertain to the following case. G.T., a 62-year-old white woman, was given a diagnosis of left breast cancer 15 years ago. At her initial diagnosis, her tumor characteristics included ER 70%; PR 65%; and HER2 negative. On physical examination, the tumor measured 2.1 cm, and the axillary lymph nodes were negative. G.T. was taken to the operating room, and a modified radical mastectomy was completed with a sentinel lymph node biopsy. Pathology revealed a 2.2-cm invasive ductal carcinoma with negative lymph nodes. In the adjuvant setting, G.T. received four courses of fluorouracil, doxorubicin, and cyclophosphamide and completed 5 years of tamoxifen therapy. G.T. has presented to the clinic with persistent bone pain during the past month. She does not recall any injuries to this area. A bone scan reveals metastatic breast cancer (MBC) in her left sixth rib. In addition to bisphosphonate therapy, which one of the following is the best regimen at this time for G.T.?

• (A) Anastrozole daily.
• (B) Paclitaxel weekly.
• (C) Tamoxifen daily.
• (D) Capecitabine twice daily.

24. G.T. did well during the next year and presented to the clinic for a yearly follow-up examination. Follow-up bone and CT scans revealed new metastases in her left femur and another metastatic site in her ribs. In addition to bisphosphonate therapy, which one of the following is the best regimen for G.T. at this time?

• (A) Fulvestrant.
• (B) Exemestane.
• (C) Tamoxifen.
• (D) Letrozole.

25. Questions 25–27 pertain to the following case. M.D., a 64-year-old woman, received a diagnosis of left breast cancer in 2000. Her cancer history includes a left modified radical mastectomy that revealed an invasive lobular carcinoma (1.5 cm, ER 63%, PR 59%, and HER2 negative) by fluorescence in situ hybridization with 2 of 15 positive axillary lymph nodes. After surgery, she received four courses of doxorubicin and cyclophosphamide, followed by four courses of every-3-week paclitaxel. Her adjuvant hormonal therapy consisted of anastrozole for 5 years. In 2007, M.D. developed metastatic disease in her right humerus and was placed on exemestane and a bisphosphonate. She continues this regimen today. M.D. returns to the clinic for a follow-up examination and is noted to have tenderness in her abdomen and a lingering pain in her right hip. A CT scan demonstrates a small 1-cm liver lesion, and a bone scan reveals a lesion in her right sacrum as well as disease in her right humerus. Her laboratory values are all within normal limits except for a CA27.29 (a tumor marker for breast cancer), which is elevated at 65 U/mL. In addition to a bisphosphonate, which one of the following is the best therapy for M.D.?

• (A) Fluoxymesterone 10 mg orally twice daily.
• (B) Ethinyl estradiol 3 mg/day orally.
• (C) Fulvestrant 250 mg intramuscularly once monthly.
• (D) Megestrol acetate 160 mg orally in divided doses daily.

26. Which one of the following should be prescribed to help prevent toxicity associated with M.D.’s bisphosphonate therapy?

• (A) Monitoring of serum calcium and creatinine.
• (B) Tooth extractions after thorough discussion with her dentist and medical oncologist.
• (C) Avoidance of endodontic and restorative dental procedures.
• (D) Prophylactic antibiotics.

27. As part of M.D.’s follow-up, in addition to CT and bone scan, which of the following tests and laboratory values are best to monitor during her treatment course?

• (A) CA27.29 and CA15.3.
• (B) CA15.3 and circulating tumor cells.
• (C) CA27.29 and brain magnetic resonance imaging (MRI).
• (D) CA15.3 and position emission tomography scan.

28. Questions 28 and 29 pertain to the following case.
C.F., a 42-year-old premenopausal woman, recently received a diagnosis of breast cancer that had metastasized to the lungs. Two years ago, C.F. received a diagnosis of stage II invasive lobular, right breast cancer. Her tumor was ER/PR negative and HER2 negative. She completed neoadjuvant chemotherapy consisting of flurouracil, doxorubicin, and cyclophosphamide for four cycles, followed by weekly paclitaxel for 12 doses. C.F. was doing well until the past month when she started experiencing shortness of breath. This kept her from walking up and down the stairs in her home and from performing normal activities of daily living. A CT scan demonstrates new nodules in both lungs, consistent with metastatic disease. Which one of the following is the best therapy for C.F. at this time?

• (A) Docetaxel plus capecitabine.
• (B) Goserelin plus anastrozole.
• (C) Liposomal doxorubicin plus vinorelbine.
• (D) Goserelin plus tamoxifen.

29. C.F. continued treatment for 8 months and tolerated therapy well. She has been monitored in the clinic monthly; today, she brings the results of repeat scans that show progression of her lung metastases. C.F. has been able to walk up and down the stairs at home with no problems. Which one of the following is the best therapy for C.F. at this time?

• (A) Gemcitabine plus paclitaxel.
• (B) Vinorelbine.
• (C) Capecitabine plus lapatinib.

30. Questions 30 and 31 pertain to the following case. N.W., a 64-year-old woman, received a diagnosis of breast cancer last year and underwent surgery and chemotherapy. She does not remember what chemotherapy she received but recalls that it was “red.” She moved recently and has been unable to obtain her records from her doctor’s office. She recently completed restaging because of increased abdominal pain. A CT scan of N.W.’s chest and abdomen revealed a 1.5-cm liver lesion. A liver biopsy was performed. The tumor is ER/PR negative and HER2 positive by fluorescence in situ hybridization. Her medical history includes hypertension, hypothyroidism, and gout. Her laboratory values today are as follows: CA27.29 = 75 U/mL and blood urea nitrogen and serum creatinine slightly elevated at 24 mg/dL and 1.2 mg/dL, respectively. Based on the new information from this biopsy, which one of the following is the best first-line treatment for N.W.’s MBC?

• (A) Capecitabine plus lapatinib.
• (B) Trastuzumab plus paclitaxel.
• (C) Trastuzumab plus liposomal doxorubicin.
• (D) Trastuzumab.

31. For 15 months, N.W. responded with stable disease. She returns to the clinic today with repeat staging consisting of CT and bone scans together with laboratory data. Her bone scan is negative; however, her CT scan shows new liver lesions. Which one of the following regimens is best for N.W. at this time?

• (A) Capecitabine plus lapatinib.
• (B) Trastuzumab.
• (C) Liposomal doxorubicin.
• (D) Gemcitabine plus paclitaxel.