chemotherapy, endocrine therapy. ⢠Maximal: dose-dense chemotherapy, growth factors. KNH, future (biology-driven). ⢠ER/PR/HER2 status, grade, molecular ...
Optimal management of non-metastatic, hormone-sensitive breast cancer in premenopausal women Ken Nkonge1, Dorothy Torutt1, Karani Nkonge1, Maureen Kamau1, Diana Nyamieri1, Sylvia Kairu1, Penninah Kabethi1, Chelsea Oprong1, Ambrose Agweyu2, Edwin Walong3 1
School of Medicine, 2 Department of Paediatrics and Child Health, and 3 Department of Human Pathology, University of Nairobi, Nairobi, Kenya.
Results
Background KNH, 2007-2008
•
FIGURE 1. Hormone-sensitive breast cancer in Kenya.
Summary of the phase III randomized controlled trials included in the present evidence-based clinical review.
ATLAS4
Of 219 patient records analyzed for estrogen receptor occurrence, 70% had no status reported
• Invasive breast cancer is a common female malignancy in Africa. Hormone-sensitive breast cancer is characterized by estrogen (ER) and/or progesterone receptor overexpression. Current data on the expression of hormone receptors among Kenyan women with breast cancer is lacking.1,2
aTTom5
Stop tamoxifen at 5 years (n = 3418)
ER+
ER-
FIGURE 2.
Cyclophosphamide
Taxanes Ovarian function Ovarian suppression ablation
• SERM • AI
Adjuvant therapies for durable control of hormone-sensitive breast cancer.3 AI = aromatase inhibitor; SERM = selective estrogen receptor modulator.
Breast cancer recurrence and breast cancer mortality
1
ZEBRA7
Leuprorelin, three-monthly for 2 years (n = 270)
Continue tamoxifen to 10 years (n = 3468)
ATLAS Trial Adapted from Davies C, et al. 20134
Breast cancer recurrence
R
Breast cancer mortality
1:1:1
CMF, 6 courses in 4-week intervals (n = 817)
Recurrence free survival; overall survival
Triptorelin (± chemotherapy) + Tamoxifen (n = 1334) Triptorelin (± chemotherapy) + Exemestane (n = 1338) TEXT total: 2672 patients
1:1
R 1:1 CMF, 6 courses in 4-week intervals (n = 256)
Breast cancer recurrence and breast cancer mortality
SOFT and TEXT8
Goserelin, every 28 days for 2 years (n = 797)
R 1:1
R 1:1
Continue tamoxifen to 10 years (n = 3428)
Not stated
TABLE6
Stop tamoxifen at 5 years (n = 3485)
R 1:1
KNH = Kenyatta National Hospital.
Anthracyclines
The proportion of ER+ breast cancer in Eastern Africa is 0.41
TABLE 1.
Conclusions
Disease-free survival and overall survival
Disease-free survival; freedom from breast cancer, freedom from distant recurrence, and overall survival
4 Subgroup
Δ 3.7% Δ 2.8%
• Retrieve peer-reviewed publications and evaluate the optimal management of non-metastatic, hormone-sensitive breast cancer in premenopausal women.
PubMed n = 73
HR
95% CI
P-value
HR
95% CI
Cochrane Library n = 50 CINAHL n=0
FIGURE 3.
Relevant publications (2000-2015) n = 123
Hormone sensitive breast cancer
Yes
Included n=6
No n = 15
Study flow diagram of search strategy used for the present evidence-based clinical review.
Ovarian suppression combination therapy n=2
Breast Health Global Initiative guidelines Basic: mastectomy, endocrine therapy, chemotherapy Limited: breast conserving surgery, radiation therapy, chemotherapy Enhanced: axillary lymphadenectomy, biological therapy, chemotherapy, endocrine therapy • Maximal: dose-dense chemotherapy, growth factors • • • •
P-value
ER+ (n = 1189)
1.01
0.84 - 1.20
0.94
0.99
0.76 - 1.28
0.92
ER- (n = 304)
1.76
1.27 – 2.44
0.0006
1.77
1.19 – 2.63
0.0043
KNH, future (biology-driven) • • • • •
aTTom Trial Breast cancer recurrence
Adapted from Gray R, et al. 20135
Breast cancer mortality
5a
SOFT and TEXT Trials
ER/PR/HER2 status, grade, molecular profile Neoadjuvant: chemotherapy, endocrine therapy Locoregional: mastectomy, lumpectomy, radiation therapy, axillary surgery Adjuvant: chemotherapy, endocrine therapy (SERM, LHRH agonists, OFS+AI) Metastatic: endocrine therapy, targeted therapy, chemotherapy
FIGURE 4.
Δ 1.0%
Tamoxifen duration n=2
Ovarian suppression monotherapy n=2
KNH, now (stage-driven)
OS
Δ 3.8%
Excluded if not analyzing adjuvant therapy n = 18
• In Kenya, tumor board reviews, prospective hospital-based cancer registries, and public-private partnerships may help guide future clinical trials design and patient recruitment
CI = confidence interval; DFS = disease-free survival; ER = estrogen receptor; HR = hazard ratio; OS = overall survival. Adapted from Jonat W, et al. 20027
2
Methods
• Extended duration of endocrine therapy and the combination of ovarian function suppression and an aromatase inhibitor are potentially practice-changing treatment options
ZEBRA Study DFS
Objectives
Excluded if not phase III RCT n = 84
OFS + Tamoxifen (n = 1024) OFS + Exemestane (n = 1021) Tamoxifen alone (n = 1021) SOFT total: 3066 patients
• Current evidence suggests that the optimal management of hormone-sensitive breast cancer is determined by patientspecific clinico-pathological characteristics and responsiveness to endocrine therapy
Future clinical implications of current findings.
Breast cancer management algorithms should be guided by predictive biomarkers.9,10
References
Adapted from Pagani O, et al. 20148
3
TABLE Study Recurrence-free survival 63.9% 63.4%
Adapted from Schmid P, et al. 20076
Overall survival
5b
SOFT and TEXT Trials
81.0% Δ 4.0%
71.9%
Adapted from Pagani O, et al. 20148
Δ 1.8%
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Eng A, McCormack V, dos-Santos-Silva I: PLoS Med 2014, 11: e1001720. Wata DE, Osanjo GO, Oluka M, Guantai AN: Afr J Pharmacol Ther 2013, 2: 109-115. Turner NC, Jones AL: BMJ 2008, 337: 164-169. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Abraham M, et al: Lancet 2013, 381: 805-816. Gray RG, Rea D, Handley K, Bowden SJ, Perry P, Earl HM, et al: aTTom: J Clin Oncol 2013: suppl; abstr 5. Schmid P, Untch M, Kossé V, Bondar G, Vassiljev L, Tarutinov V, et al: J Clin Oncol 2007, 25: 2509-2515. Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, et al: J Clin Oncol 2002, 20: 4628-4635. Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, et al: N Engl J Med 2014, 371: 107-118. Eniu A, Carlson RW, El Saghir NS, Bines J, Bese NS, Vorobiof D, et al: Cancer 2008, 113: 2269-2281. Toss A, Cristofanilli M: Breast Cancer Res 2015, 17: 60.
