Breast Cancer (Invasive; Nonmetastatic) Treatment Regimens

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Breast Cancer (Invasive; Nonmetastatic) Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

Adjuvant Endocrine Therapy1

REGIMEN

DOSING

Hormone Receptor-Positive Disease

Premenopausal at diagnosis

Tamoxifen (with or without Leuprolide or Goserelin) followed by Aromatase Inhibitor2-15

Tamoxifena 20mg orally once daily for 5 years (Category 1) with or without

Day 1: Leuprolideb 3.75mg IM of 28-day cycle (Category 1) OR

Day 1: Goserelinb 3.6mg subcutaneous of 28-day cycle (Category 1)

followed by (for post-menopausal women)

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily for 5 years (Category 1).

Tamoxifen (with or without Leuprolide or Goserelin)2,6-14,16

Tamoxifena 20mg orally once daily for 5 years (Category 1), with or without

Day 1: Leuprolideb 3.75mg IM of 28-day cycle (Category 1) OR

Day 1: Goserelinb 3.6mg subcutaneous of 28-day cycle (Category 1)

Tamoxifen (with or without Leuprolide or Goserelin) followed by consideration of Tamoxifen2,6-14,16

Tamoxifena 20mg orally once daily for 5 years (Category 1) with or without

Day 1: Leuprolideb 3.75mg IM of 28-day cycle (Category 1) OR

Day 1: Goserelinb 3.6mg subcutaneous of 28-day cycle (Category 1)

followed by (for pre- or postmenopausal women)

Tamoxifena 20mg orally once daily for an additional 5 years.

Aromatase inhibitor (with Leuprolide or Goserelin)3-14,17,18

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily for 5 years (Category 1) AND

Day 1: Leuprolideb 3.75mg IM of 28-day cycle(Category 1) OR

Day 1: Goserelinb 3.6mg SC of 28-day cycle (Category 1).

Postmenopausal at diagnosis

Aromatase inhibitor followed by consideration of an Aromatase Inhibitor3-5,18-23

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily for 5 years (Category 1) followed by

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily for an additional 5 years.

Aromatase inhibitor followed by Tamoxifen2-4, 25

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily for 2 to 3 years (Category 1) followed by

Tamoxifena 20mg orally once daily to complete 5 years of endocrine therapy (Category 1).

Tamoxifen followed by an Aromatase Inhibitor2-5,26-42

Tamoxifena 20mg orally once daily for 2 to 3 years followed by

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily to complete 5 years of endocrine therapy (Category 1).

Tamoxifena 20mg orally once daily for 2 to 3 years followed by

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily for up to 5 years of an aromatase inhibitor (Category 2B).

Tamoxifena 20mg orally once daily for 4 to 6.5 years followed by

Anastrozolec 1mg orally once daily OR

Exemestanec 25mg orally once daily OR

Letrozolec 2.5mg orally once daily for 5 years (Category 1).

Tamoxifen followed by consideration of Tamoxifen2,8,16

Tamoxifena 20mg orally once daily for 4 to 6.5 years followed by

Tamoxifena 20mg orally once daily to complete 10 years of endocrine therapy.

Postmenopausal patients with contraindication to aromatase inhibitors or who cannot tolerate or decline aromatase inhibitor

Tamoxifen2,8,16

Tamoxifena 20mg orally once daily for 5 years (Category 1).

Tamoxifena 20mg orally once daily for up to 10 years.

Neoadjuvant/Adjuvant Chemotherapy1,d-j

HER2-negative Disease

Preferred Regimens

Dose-dense AC followed by paclitaxel (Category 1)43,k,l

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 14 days for 4 cycles (all cycles are with myeloid growth factor support; refer to NCCN Guidelines for Myeloid Growth Factors), followed by

Day 1: Paclitaxel 175mg/m2 via 3-hour IV infusion.

Repeat cycle every 14 days for 4 cycles.

All cycles are with myeloid growth factor support.

Dose-dense AC followed by weekly paclitaxel (Category 1)43,k,i

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 14 days for 4 cycles, followed by

Day 1: Paclitaxel 80mg/m2 via 1-hour IV infusion weekly for 12 weeks.

All cycles are with myeloid growth factor support.

TC (Category 1)44,l

Day 1: Docetaxel 75mg/m2 IV over 60 minutes

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 4 cycles.

All cycles are with myeloid growth factor support.

Capecitabine (if triple-negative breast cancer and residual disease after preopera­tive therapy with taxane-, alkylator-, and anthracycline-based chemotherapy. Category 1)45

Days 1-14: Capecitabine 1000-1250mg/m2 orally twice daily every 21 days for 6-8 cycles.

Useful in Certain Circumstances

Dose-dense AC (Category 1)43,l

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV.

Repeat cycle every 14 days for 4 cycles.

All cycles are with myeloid growth factor support.

AC followed by weekly paclitaxel (Category 1)46

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 4 cycles, followed by

Day 1: Paclitaxel 80mg/m2 by 1-hour IV infusion weekly for 12 weeks.

CMF (Category 1)47

Days 1–14: Cyclophosphamide 100mg/m2 orally

Days 1 and 8: Methotrexate 40mg/m2 IV push

Days 1 and 8: Fluorouracil 600mg/m2 IV push.

Repeat cycle every 28 days for 6 cycles.

AC (Category 2B)48

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 4 cycles.

Other Recommended Regimens

AC followed by docetaxel (Category 1)49

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 4 cycles, followed by

Day 1: Docetaxel 100mg/m2 IV over 60 minutes.

Repeat cycle every 21 days for 4 cycles.

EC (Category 1)50

Day 1: Epirubicin 100mg/m2 IV push

Day 1: Cyclophosphamide 830mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 8 cycles.

TAC (Category 1)51,l

Day 1: Docetaxel 75mg/m2 IV over 60 minutes

Day 1: Doxorubicin 50mg/m2 IV push

Day 1: Cyclophosphamide 500mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 6 cycles.

All cycles are with myeloid growth factor support.

HER2-positive Diseasem

Preferred Regimensn,o

AC followed by paclitaxel + trastuzumab58,59,p,q

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 4 cycles, followed by

Day 1: Paclitaxel 80mg/m2 via 1-hour IV infusion weekly for 12 weeks, with

Day 1: Trastuzumab 4mg/kg IV over 90 minutes with first dose of paclitaxel, then 2mg/kg IV over 30 minutes weekly to complete 1 year of trastuzumab therapy.

As an alternative, trastuzumab 6mg/kg IV over 30 minutes every 21 days may be used following the completion of paclitaxel, and given to complete 1 year of trastuzumab treatment.

AC followed by paclitaxel + trastuzumab + pertuzumab58-60,p,q

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Repeat cycle every 21 days for 4 cycles, followed by

Day 1: Pertuzumab 840mg IV over 60 minutes for cycle 1, then 420mg IV over 30 minutes for cycles 2-4

Day 1: Trastuzumab 8mg/kg IV over 90 minutes for cycle 1, then 6mg/kg IV over 30 minutes for cycles 2-4

Days 1, 8, and 15: Paclitaxel 80mg/m2 IV over 60 minutes.

Repeat cycle every 21 days for 4 cycles, followed by

Day 1: Trastuzumab 6mg/kg IV over 30 minutes

Day 1: Pertuzumab 420 mg IV over 30 minutes.

Repeat cycle every 21 days to complete 1 year of trastuzumab and pertuzumab therapy.

Dose-dense AC followed by paclitaxel + trastuzumab58,61,l,p,q

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes

Repeat cycle every 14 days for 4 cycles, followed by

Day 1: Paclitaxel 175mg/m2 via 3-hour IV infusion.

Cycled every 14 days for 4 cycles, with

Day 1: Trastuzumab 4mg/kg IV over 90 minutes with first dose of paclitaxel, then 2mg/kg IV over 30 minutes weekly to complete 1 year of trastuzumab therapy.

As an alternative, trastuzumab 6mg/kg IV over 30 minutes every 21 days may be used following the completion of paclitaxel, and given to complete 1 year of trastuzumab treatment.

All cycles are with myeloid growth factor support.

Paclitaxel + trastuzumab58,62,r

Day 1: Paclitaxel 80mg/m2 IV over 60 minutes weekly for 12 weeks with

Day 1: Trastuzumab 4mg/kg IV over 90 minutes with first dose of paclitaxel, then 2 mg/kg IV over 30 minutes weekly to complete 1 year of trastuzumab therapy OR

Day 1: Trastuzumab 6mg/kg IV over 30 minutes every 21 days to complete 1 year of trastuzumab therapy following the completion of paclitaxel.

TCH58,63,l,q

Day 1: Trastuzumab 4mg/kg IV over 90 minutes for cycle 1, then 2mg/kg IV over 30 minutes weekly to complete 18 cycles, with

Day 1: Docetaxel 75mg/m2 IV over 60 minutes, with

Day 1: Carboplatin AUC 6 IV over 30 minutes cycled every 21 days for 6 cycles, followed by

Day 1: Trastuzumab 6mg/kg IV over 30 minutes every 21 days to complete 1 year of trastuzumab therapy.

As an alternative, trastuzumab 8mg/m2 IV over 90 minutes may be used on day 1 of cycle 1, then 6mg/kg IV over 30 minutes to complete 1 year of trastuzumab therapy.

All cycles are wtih myeloid growth factor support.

TCH + pertuzumab58,60,64,l,q

Day 1: Trastuzumab 8mg/kg IV over 90 minutes for cycle 1, then 6mg/kg IV over 30 minutes every 21 days for cycles 2-6

Day 1: Pertuzumab 840mg IV over 60 minutes for cycle 1, then 420 mg IV over 30 minutes every 21 days for cycles 2-6

Day 1: Docetaxel 75mg/m2 IV over 60 minutes

Day 1: Carboplatin AUC 6 IV over 30 minutes.

Repeat cycle every 21 days for cycles 1-6, followed by

Day 1: Trastuzumab 6mg/kg IV over 30 minutes every 21 days to complete 1 year of trastuzumab therapy

Day 1: Pertuzumab 420mg IV over 30 minutes to complete 1 year of pertuzumab therapy.

All cycles are with myeloid growth factor support.

Useful in Certain Circumstances

Docetaxel + cyclophosphamide + trastuzumab58,65,q,r

Day 1: Docetaxel 75mg/m2 IV over 60 minutes

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Cycled every 21 days for 4 cycles, with

Day 1: Trastuzumab 4mg/kg IV over 90 minutes week 1, then 2mg/kg IV over 30 minutes weekly for 11 weeks, then 6mg/kg every 21 days to complete 1 year of trastuzumab therapy OR

Day 1: Trastuzumab 8mg/kg IV over 90 minutes cycle 1, then 6mg/kg IV over 30 minutes every 21 days to complete 1 year of trastuzumab therapy.

Other Recommended Regimens

AC followed by docetaxel + trastuzumab58,62,66,p,q

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV over 30 minutes.

Cycled every 21 days for 4 cycles, followed by

Day 1: Docetaxel 100mg/m2 IV over 60 minutes.

Cycled every 21 days for 4 cycles, with

Day 1: Trastuzumab 4mg/kg IV over 90 minutes week 1, then 2mg/kg IV over 30 minutes weekly for weeks 2-12, then 6mg/kg IV over 30 minutes every 21 days to complete 1 year of trastuzumab therapy.

AC followed by docetaxel + trastuzumab + pertuzumab58,60,67,p,q

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Cyclophosphamide 600mg/m2 IV 0ver 30 minutes.

Repeat cycle every 21 days for 4 cycles, followed by

Day 1: Pertuzumab 840mg IV over 60 minutes for cycle 1, then 420mg IV over 30 minutes for cycles 2-4

Day 1: Trastuzumab 8mg/kg IV over 90 minutes for cycle 1, then 6mg/kg IV over 30 minutes for cycles 2-4 followed by

Day 1: Docetaxel 75mg/m2 IV over 60 minutes for cycle 1, then 100mg/m2 IV over 60 minutes for cycles 2-4 (if tolerated).

Repeat cycle every 21 days for 4 cycles, followed by

Day 1: Trastuzumab 6mg/kg IV over 30 minutes and Pertuzumab 420 mg IV over 30 minutes every 21 days to complete 1 year of trastuzumab and pertuzumab therapy.

a   Some SSRIs like fluoxetine and paroxetine decrease the formation of impact its efficacy. Caution is advised about coadministration of these drugs with tamoxifen. However, citalopram and venlafaxine appear to have minimal impact on tamoxifen metabolism. At this time, based on current data the panel recommends against CYP2D6 gene testing for women being considered for tamoxifen therapy. Coadministration of strong inhibitors of CYP2D6 should be used with caution.

b   A balanced discussion of the risk and benefits associated with ovarian suppression therapy is critical. Aromatase inhibitor or tamoxifen for 5 years plus ovarian suppression should be considered, based on SOFT and TEXT clinical trial outcomes, for premenopausal women at higher risk of recurrence (ie, young age, high-grade tumor, lymph node involvement).

c   The three selective aromatase inhibitors (ie, anastrozole, letrozole, exemestane) have shown similar anti-tumor efficacy and toxicity profiles in randomized studies in the adjuvant and preoperative settings. The optimal duration of aromatase inhibitors in adjuvant therapy is uncertain.

d   The selection, dosing, and administration of anticancer agents and the management of associated toxicities are complex. Modifications of drug dose and schedule and initiation of supportive care interventions are often necessary because of expected toxicities and individual patient variability, prior treatment, and comorbidity. The optimal delivery of anticancer agents therefore requires a healthcare delivery team experienced in the use of anticancer agents and the management of associated toxicities in patients with cancer.

e   Retrospective evidence suggests that anthracycline-based chemotherapy regimens may be superior to nonanthracycline-based regimens in patients with HER2-positive tumors.

f   Randomized clinical trials demonstrate that the addition of a taxane to anthracycline-based chemotherapy provides an improved outcome.

g   CMF and radiation therapy may be given concurrently, or the CMF may be given first. All other chemotherapy regimens should be given prior to radiotherapy. h   Chemotherapy and endocrine therapy used as adjuvant therapy should be given sequentially with endocrine therapy following chemotherapy.

i   Nab-paclitaxel may be substituted for paclitaxel or docetaxel due to medical necessity (ie, hypersensitivity reaction). If substituted for weekly paclitaxel or docetaxel, then the weekly dose of nab-paclitaxel should not exceed 125mg/m2.

j   Consider scalp cooling to reduce incidence of chemotherapy-induced alopecia for patients receiving neoadjuvant/adjuvant chemotherapy. Results may be less effective with anthracycline- containing regimens.

k   It would be acceptable to change the administration sequence to paclitaxel followed by dose-dense AC.

l    All cycles are with myeloid growth factor.

m  Trastuzumab and hyaluronidase-oysk injection for subcutaneous use may be substituted for trastuzumab.52,53 It has different dosing and administration instructions compared to intravenous trastuzumab. Do not substitute trastuzumab and hyaluronidase-oysk for or with ado-trastuzumab emtansine. (Trastuzumab and hyaluronidase-oysk 600mg subcutaneous over 2-5 minutes. Cycle length is regimen specific. Trastuzumab and hyalruonidase-oysk is administered as a substitute for intravenous trastuzumab on the days that intravenous trastuzumab is administered as per the regimen. This agent dose not require a loading dose. No dose adjustments for patient body weight or for different concomitant chemotherapy are required). An FDA-approved biosimilar is an appropriate substitute for trastuzumab.

n  If no residual disease after preoperative therapy or no preoperative therapy: Complete up to one year of HER2-targeted therapy with trastuzumab (Category 1) +/- pertuzumab. Consider extended neratinib (Neratinib 240mg orally once daily for 1 year following adjuvant trastuzumab-containing therapy for patients with hormone receptor-positive, HER2-positive disease with a perceived high risk of recurrence).54,55 The benefit or toxicities associated with extended neratinib in patients who have received pertuzumab or ado-trastuzumab emtansine is unknown.

o  If residual disease after preoperative therapy: Ado-trastuzumab emtansine alone (Category 1; Ado-trastuzumab emtansine 3.6mg/kg IV every 21 days for 14 cycles. If ado-trastuzumab emtansine discontinued for toxicity, then trastuzumab (Category 1) +/- pertuzumab to complete one year of therapy.56,57 Consider ex­tended neratinib (Neratinib 240mg orally once daily for 1 year following adjuvant trastuzumab-containing therapy for patients with hormone receptor-posi­tive, HER2-positive disease with a perceived high risk of recurrence).54,55 The benefit or toxicities associated with extended neratinib in patients who have received pertuzumab or ado-trastu­zumab emtansine is unknown.

p  Trastuzumab given in combination with an anthracycline is associated with significant cardiac toxicity. Concurrent use of trastuzumab and pertuzumab with an anthracycline should be avoided.

 q  Evaluate left ventricular ejection fraction (LVEF) before and during treatment. Although the optimal frequency of LVEF assessment during adjuvant trastuzumab therapy is not known, the FDA label recommends LVEF measurements every 3 months during treatment.

r   Paclitaxel + trastuzumab may be considered for patients with low-risk, T1, N0, M0, HER2-positive disease, particularly those not eligible for other standard adjuvant regimens due to comorbidities.

References

 1.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.3.2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed October 17, 2019.

 2.  Tamoxifen (Novadex) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2004.

 3.  Letrozole (Femara) [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corp.; 2017.

 4.  Anastrozole (Arimidex) [package insert]. Baudetter, IL: Ani Pharmaceuticals Inc.; 2018.

 5.  Exemestane (Aromasin) [package insert]. New York, NY: Pfizer Pharmaceutical Co.; 2018.

 6.  Leuprolide (Lupron) [package insert]. North Chicago, IL: AbbVie, Inc.; 2018.

 7.  Goserelin (Zoladex) [package insert]. Lake Forest, IL: TerSera Therapeutics LLC; 2017.

 8.  Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet. 2005;365:1687-1717.

 9.  Baum M, Hackshaw A, Houghton J, et al. Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study. Eur J Cancer. 2006;42:895-904.

10. Boccardo F, Rubagotti A, Amoroso D, et al. Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breast cancer patients. Cancer Chemother Pharmacol. 1999;43:461-466.

11. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of clinical oncology clinical practice guideline update on ovarian suppression. J Clin Oncol. 2016;34:1689-701.

12. Klijn JG, Blamey RW, Boccardo F, et al. Combined tamoxifen and luteinizing hormone- releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Onol. 2001;19:343-353.

13. Cuzick J, Ambroisine L, Davidson N, et al. Use of luteinizing-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomized adjuvant trials. Lancet. 2007;369:1711-1723.

14. Francis PA, Pagani O, Fleming GF, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379:122-137.

15. Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, et al. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst. 2018;110(1).

16. Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer.: ATLAS, a randomized trial. Lancet. 2013;381:805-816.

17. Torrisi R, Bagnardi V, Rotmensz N, et al. Letrozole plus GnRN analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer. Breast Cancer Res Treat. 2011;126:431-441.

18. Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal women. N Engl J Med. 2014;371:107-118.

19. Baum M, Budzar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet. 2002;359:2131-2139.

20. Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365:60-62.

21. Thurlimann B, Keshaviah A, Coates AS, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353:2747-2757.

22. Paridaens RJ, Dirix LY, Beex LV, et al. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer with postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol. 2008;26:4883-4890.

23. Ellis MJ, Suman VJ, Hoog J, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 or 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype –ACOSOG Z1031. J Clin Oncol. 2011;29:2342-2349.

24. Dowsett M, Cuzick J, Ingle J, et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010;28:509-518.

25. Thürlimann B, Robertson JF, Nabholtz JM, et al. Efficacy of tamoxifen following anastrozole (‘Arimidex’) compared with anastrozole following tamoxifen as first-line treatment for advanced breast cancer in postmenopausal women. Eur J Cancer. 2003;39:2310-2317.

26. Cuzick J, Sestak I, Baum M, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010;11:1135-1141.

27. Mouridsen H, Giobbie-Hurder A, Goldhirsch A, et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med. 2009;361:766-776.

28. Kaufmann M, Jonat W, Hilfrich J, et al. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007;25:2664-2670.

29. Van de Velde CJ, Rea D, Seynaeve C, et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomized phase 3 trial. Lancet. 2011;377:321-331.

30. Jonat W, Gnant M, Boccardo F, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. Lancet Oncol. 2006;7:991-996.

31. Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two or three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350:1081-1092.

32. Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366:455-462.

33. Jakesz R, Greil R, Gnant M, et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007;99:1845-1853.

34. Muss HB, Tu D, Ingle NJ, et al. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG Intergroup trial MA.17. J Clin Oncol. 2008;26:1956-1964.

35. Ingle JN, Tu D, Pater JL, et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17. Ann Oncol. 2008;19:877-882.

36. Goss PE, Ingle JN, Martino S, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA,17. J Natl Cancer Inst. 2005;97:1262-1271.

37. Goss PE, Ingle JN, Pater JL, et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008;26:1948-1955.

38. Mamounas EP, Jeong JH, Wickerham DL, et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008;26:1965-1971.

39. Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM, et al. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol. 2017;18:1502-1511.

40. Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, et al. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; Results of the IDEAL Trial (BOOG 2006-05). J Natl Cancer Inst. 2018;110(1).

41. Colleoni M, Luo W, Karlsson P, et al. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal womenwith breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19: 127-138.

42. De Placido S, Gallo C, De Laurentiis M, et al. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine- sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018;19:474-485.

43. Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21(8):1431–1439. Erratum in: J Clin Oncol. 2003; 21(11):2226.

44. Jones S, Holmes F, O’Shaughnessey J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research trial 9735. J Clin Oncol. 2009;27(8):1177–1183.

45. Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376:2147-2159.

46. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in adjuvant treatment of breast cancer. N Engl J Med. 2008; 358:1663–1671.

47. Goldhirsch A, Colleoni M, Coates AS, et al. Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol. 1998;9:489–493.

48. Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with six months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from NSABP B-15. J Clin Oncol. 1990;8:1483–1496.

49. von Minckwitz G, Raab G, Caputo A, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005;23:2676–2685.

50. Piccart MJ, Di Leo A, Beauduin M, et al. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001;19:3103–3110.

51. Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352:2302–2313.

52. Trastuzumab and hyaluronidase-oysk (Herceptin Hylecta) [package insert]. South San Francisco, CA: Genentech, Inc.; 2019.

53. Gligorov J, Ataseven B, Verrill M, et al. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study’s primary analysis of 2573 patients. Eur J Cancer. 2017;82:237-246.

54. Neratinib (Nerlynx) [package insert]. Los Angeles, CA: Puma Biotechnology, Inc.; 2018.

55. Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17:367-77.

56. Ado-trastuzumab emtansine (Kadcyla) [package insert]. South San Francisco, CA: Genentech, Inc.; 2018.

57. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380:617-628.

58. Trastuzmab (Herceptin) [package insert]. South San Francisco, CA: Genentech, Inc.; 2018.

59. Romond EH, Perez EZ, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2 positive breast cancer. N Engl J Med. 2005;353:1673–1684

60. Pertuzumab (Perjeta) [package insert]. South San Francisco, CA: Genentech, Inc.; 2018.

61. Dang C, Fornier M, Sugarman S, et al. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008;26:1216–1222.

62. Tolaney S, Barry W, Dang C, et al. Adjuvant paclitaxel and trastuzumab for node- negative HER2-positive breast cancer. N Engl J Med. 2015;372:134-141.

63. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–1283.

64. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in com­bi­na­tion with standard neoadjuvant anthracycline–containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24:2278–2284.

65. Jones SE, Collea R, Paul D, et al. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013;14:1121–1128.

66. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354:809-820.

67. von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer N Engl J Med. 2017.

(Revised 10/2019) © 2019 by Haymarket Media, Inc.

Breast Cancer Drug Monographs

Breast Cancer

ABRAXANE AFINITOR ARIMIDEX
AROMASIN Cyclophosphamide CYTOXAN INJECTION
DELATESTRYL Doxorubicin HCl Doxorubicin HCl Solution
ELLENCE ESTRACE EVISTA
FARESTON FASLODEX FEMARA
Fluorouracil Fluoxymesterone GEMZAR
HALAVEN HERCEPTIN IBRANCE
IXEMPRA KADCYLA KISQALI
Megestrol acetate Methotrexate for injection Methotrexate injection
Pamidronate disodium Injection PERJETA PREMARIN
SOLTAMOX ORAL SOLUTION Tamoxifen TAXOL
TAXOTERE Thiotepa TREXALL
TYKERB Vinblastine for injection Vinblastine injection
XELODA ZOLADEX
Data provided by MPR.