pm 1.30 stefanick

40
The Women’s Health Initiative (WHI) What Have We Learned? Marcia L. Stefanick, Ph.D. Professor of Medicine Stanford Prevention Research Center Professor of Obstetrics & Gynecology Stanford University School of Medicine The Vivian Pinn Women's Health Research Keynote Lecture - March 16, 2012

Upload: plmiami

Post on 02-Nov-2014

346 views

Category:

Health & Medicine


1 download

DESCRIPTION

 

TRANSCRIPT

Page 1: Pm 1.30 stefanick

The Women’s Health Initiative (WHI)

What Have We Learned?

Marcia L. Stefanick, Ph.D. Professor of Medicine

Stanford Prevention Research Center

Professor of Obstetrics & GynecologyStanford University School of Medicine

The Vivian Pinn Women's Health Research Keynote Lecture - March 16, 2012

Page 2: Pm 1.30 stefanick

DISCLOSURE

I have nothing to disclose

Marcia L. Stefanick, Ph.D. Professor of Medicine, Stanford Prevention Research Center

Professor of Obstetrics & GynecologyStanford University School of Medicine

Page 3: Pm 1.30 stefanick

Women’s Health Initiative (WHI) Clinical Trials

(Diet, Hormones, Calcium/Vit D) and Observational Study

Postmenopausal Women

aged 50-79 yrs (1993-1998)Residing in area (likely to survive) ≥ 3 yrs

Conducted at 40 Clinical Centers+ Clinical Coordinating Center

(Fred Hutchinson Cancer Research Center)

EXTENSIONS: 2005-2010, 2010-2015

Funded by National Institutes of HealthNational Heart, Lung, and Blood Institute

www.whi.orgwww.whiscience.org

Page 4: Pm 1.30 stefanick
Page 5: Pm 1.30 stefanick

WHI Clinical Trials

Postmenopausal Women, aged 50-79; Not moving < 3 yrs

Diet Modification (DM) Trial Primary Outcomes: Breast & Colorectal Cancer Secondary Outcome: Coronary Heart Disease (CHD)

Hormone Trials Primary Outcome: CHD Secondary Outcomes: Hip Fracture, Breast Cancer Ancillary Study: Memory (Dementia)

11.8% Overlap

Design ~ 9 years average

follow-up

Hormone27, 347(50:50)

Diet (DM)48,836(40:60)

Total CT = 68,133

Page 6: Pm 1.30 stefanick

OS93, 676

Total WHI Sample (CT + OS) = 161,809

WHI: Observational Study (OS) Women screened for the DM or HT trials could enroll in the OS, if ineligible for the CT, or chose not to join either DM or HT trials. Some women enrolled directly in the OS.

Annual Questionnaires

Purpose of OS:secular control for the CTimprove risk prediction for primary outcomescase-control approach to study

sub-clinical markers for diseaseassociations between genetic, biochemical,

psychosocial, physiological factors and eventsimpact of changes in risk factors on incident disease and mortality

Page 7: Pm 1.30 stefanick

WHI Clinical Trials and Observational Study Timeline: 1991 – 2011

WHI Begins

Observational Study

Begins

Diet and Hormone Trials

Recruitment completed

Estrogen + Progestin (E+P) Trial Stopped for Harm > Benefit

JAMA 2002

DM, CaD Trials:Closeout visits

completed

DM Results .JAMA 2006

CaD ResultsNEJM 2006

Diet and Hormone

Clinical Trials Begin

Observational Study

Recruitment completed

WHI EXTENSION 2005-2010 BEGINS

Observational Study

Year 3 clinic visits complete

Calcium plus Vitamin D

Clinical Trial Begins Estrogen only

Trial: stoppedJAMA 2004

1991 92 93 94 95 96 97 98 99 2000 2001 2002 03 2004 2005 06 07 08 09 2010

E+P Post-stopping (2.4 yrs)

JAMA 2011

E only Post-stopping

JAMA 2011

2011

WHI EXTENSION 2

2010-2015 BEGINS

Page 8: Pm 1.30 stefanick

WHI Diet Trial: Sample Size, Key Outcomes; Criteria:Postmenopausal Women, aged 50-79; Not moving < 3 yrs

Excluded if % Energy from Fat < 32% by Food Frequency Questionnaire (FFQ) History of Breast or

Colorectal Cancer

Dietary Change Goals 20% energy from fat

≥ 5 vegetable & fruit servings per day

≥ 6 grain servings daily NO Weight Change Goals

Intervention: N = 19,541Comparison: N = 29,294

Design ~ 9 years average

follow-up

Diet (DM)48,836(40:60)

Page 9: Pm 1.30 stefanick

WHI Diet Trial: INVASIVE BREAST CANCERN=48,325; 8.1 yrs follow-up HR 0.91 (95% CI: 0.83-

1.01)

JAMA 2006; 295; 629-642

1,727 total diagnoses (3.5% of all DM participants)

9% (not significant)

Invasive Breast Cancer

Cumulative Hazard

0 1 2 3 4 5 6 7 8 9

Time (years)0.00

0.01

0.02

0.03

0.04

ComparisonIntervention

HR, 0.91(95% CI, 0.83-1.01)

Events

Intervention 47 79 92 80 72 94 89 46 33

Comparison 74 140 123 137 136 137 145 97 58

Number at Risk

Intervention 19541 19328 19084 18798 18520 18263 17900 15507 10245 5075

Comparison 29294 28908 28536 28195 27806 27372 26977 23337 15373 7580

Rates per 10,000/yearCumulative Hazard Ratio

Page 10: Pm 1.30 stefanick

INVASIVE BREAST CANCER

1,727 total diagnoses (3.5% ppts) HR 0.91 (95% CI: 0.83-1.01)

There was a significant interaction of diet assignment with baseline % calories from fat, by quartile (p=0.04):

Women who consumed highest % fat at baseline (≥ 36.8%) had significant 22% reduction in invasive breast cancer if assigned to DIET vs Control

(HR: 0.78; 95% CI: 0.64,0.95).

JAMA 2006; 295; 629-642

COLORECTAL CANCER 480 total diagnoses (1% of ppts) HR 1.08 (95% CI: 0.90-1.29)

Self-reported polyps & adenomas HR 0.91 (95% CI: 0.87-0.95)

JAMA 2006; 295; 643-654

Figure 3. Change* from Baseline to Year 1 in the Intervention Compared to the Comparison Group for Blood Hormone Concentrations Adjusted for Baseline

Differences

0.85

0.98

0.96

0.99

1.09

0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6

Estradiol

Estrone

Estrone-sulfate

Testosterone

Sex Hormone Binding Globulin

Change Estimate and 95% Confidence Interval

Relative 1 Yr Hormone Changes (Subsample)

E2

E1

SHBG

T

Estrone Sulfate

WHI Diet Trial: PRIMARY CANCER OUTCOMESN=48,325; 8.1 yrs follow-up

Page 11: Pm 1.30 stefanick

WHI Calcium Vitamin D Trial: Relationship to CT

Primary Outcome: Hip Fracture Secondary Outcomes: Colorectal Cancer; Other Fractures

CaD36,282 at 1st (or 2nd)

Annual Visit

1000 mg calcium carbonate +

400 IU vitamin D*

Diet (DM) 25,210

of 48,836 (52%)

Hormone16,089

of 27,347 (59%)

Placebo

53.3% of CT

* 1/2 (i.e. 500 mg Ca + 200 IU Vit D) AM, 1/2 PMChoice: Chewable or Swallowable Pills

Hip Fracture: 12% decrease (not significant) 21% significant decrease for ages 60-80

Colorectal Cancer: no benefitKidney Stones: increased 17% (significant)

Page 12: Pm 1.30 stefanick

Women’s Health Initiative (WHI) Hormone Therapy (HT) Trials

Hysterectomy

CEE (Conjugated equine estrogens, 0.625 mg/d)

CEE + MPA (medroxy-progesterone acetate, 2.5 mg/d)

NO N= 16,608

YESN= 10,739

Placebo

Placebo = Premarin®

= Prempro®

E-alone Trial

E+P TrialGenerally HealthyPostmenopausal

Women aged 50-79 years

*Initially: CEE only (N=331), CEE+MPA, or Placebo (Post-PEPI: CEE only were converted to CEE+MPA) Current HT required 3-month wash-out before baseline testing.

Page 13: Pm 1.30 stefanick

E-Alone10,739

WHI HT Trials: Sample Size, Outcomes, Follow-up

Women, aged 50-79 Total HT trials = 27,347

Hormone Trials Primary Outcome: Coronary Heart Disease Secondary Outcomes:

WHI Memory Study (WHIMS) - for women aged ≥ 65: Dementia

Average Follow-up 5.6 years*

Average

7.1 years*

E+P16,608

*design ~ 8.5 years

Stroke, Blood Clots Lungs (PE, pulmonary emboli) Legs (DVT, deep vein thrombosis)

Breast, Colorectal, Uterine CancersHip Fracture; Other Deaths

Page 14: Pm 1.30 stefanick

Stroke?

Threshold LevelEarly STOPPING

for HARM

Threshold Level Early STOPPING

for BENEFIT

Coronary Artery Disease(Heart Attacks)

Breast Cancer

Anticipated Risk Expected Benefit

Plan to follow to 2005 (average 8.5 years)

Additional Benefits:• Hip (Bone) Fractures• Overall Mortality

Additional Risks:• Blood Clots, VTE

Lungs=PE; Legs=DVT

WHI Hormone Trials: Baseline Hypotheses

• Colon Cancer• Global Index: overall balance of benefits and risks Earliest occurrence of CHD, Stroke, PE, Breast Cancer, Hip Fracture, Colorectal Cancer, Death from other causes, Endometrial Cancer

Page 15: Pm 1.30 stefanick

05

101520253035

50-54 55-59 60-64 65-69 70-74 75-79

Percent

Intact Uterus:E+P Hysterectomy: CEE only

WHI HT: Baseline Age DistributionMean (SD): E+P Trial = 63.3(7.1) E-Alone Trial = 63.6 (7.3)

60-69E+P 45%

E-alone 45%

70-79 E+P 22%

E-alone 24%

50-59E+P 33%

E-alone 31%

Stefanick, Cochrane, Hsia, Barad, Liu, Johnson Ann Epidemiol 2003; 13: S78-S86

Goal: 50-54: 10%55-59: 20% 60-69: 45% 70-79: 25%

Page 16: Pm 1.30 stefanick

WHI Hormone Trials: Ethnic Distribution by Age

50-59 60-69 70-79

E+P 21.5% E+P 12.5% E+P 8.6% E-Alone 32.7% E-Alone 22.0% E-Alone 13.9%

10 9

64

2

20

54

2

10

14

10

0

5

10

15

20

25

Black Hispanic Black Hispanic Black Hispanic

Percent

Uterus - E+P (84.0 % White ) Hysterectomy- E only (75.3% White)

Stefanick, Cochrane, Hsia, Barad, Liu, Johnson Ann Epidemiol 2003; 13: S78-S86

Page 17: Pm 1.30 stefanick

26% Increase Breast Cancer

Also: DVTs

STOPPED Early, Clear Harm

Threshold Level

Risks

Benefits

*Adapted from: Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333

Stopped 3.3 yrs early* had 0.4 more yrs of data

WHI E+P Trial: Preliminary* Findings, July 2002 (*aver. 5.2 yrs)

Other Fractures

Page 18: Pm 1.30 stefanick

26% Increase Breast Cancer

Also: DVTs

33% Decrease Hip Fracture

STOPPED Early, Clear Harm

Threshold Level

29% Increase CHD (Coronary Heart Disease)

41% Increase Stroke

Risks

Benefits

*Adapted from: Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333

Stopped 3.3 yrs early* had 0.4 more yrs of data

113% Increase Pulmonary Emboli

Fewer Colorectal Cancers

Other Fractures

WHI E+P Trial: Preliminary* Findings, July 2002 (*aver. 5.2 yrs)

Page 19: Pm 1.30 stefanick

PlaceboE + P

Deaths

Neutral

Nu

mb

er o

f C

ases

per

10,

000

Wo

men

per

Yea

r

60

50

40

30

20

10

0 CHD* Stroke* BreastCancer

PE* ColorectalCancer*

HipFracture*

EndometrialCancer

Risks*

7 8 8 8Additional Events

6 5

Reduced

Events

*Statistically significant based on 95% nominal CI on Hazard Ratios

Adapted from: Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333

WHI E+P Trial: Absolute (annualized) Risk (5.2 Yrs*)*Preliminary Findings

Page 20: Pm 1.30 stefanick

E-Alone (post-hystX)

2947

WHI Memory Study (WHIMS) - ancillary study

(Postmenopausal Women, aged ≥ 65 yrs)

WHIMS E+P and E-only trials = 7,479

Primary Outcome: Probable Dementia (PD)

Secondary Outcomes: Combined PD & Mild Cognitive

Impairment (MCI)- Supporting Data: Global Cognitive Function

(by annual Modified Mini-mental State Examination, 3MSE))

Average Follow-up 4.1 years*

Average

5.2 years*

E+P (women with a uterus)

4532

*design ~ 7 years

Page 21: Pm 1.30 stefanick

Years Since Randomization

Cum

ulat

ive

Haz

ard

HR, 2.0595% CI, 1.21__3.48

WHIMS E+P: Probable Dementia Hazard Ratio

4532 women, aged 65-80; followed for 4.1 years

E+PPlacebo

No. at Risk

E+P

Placebo

2229 2112 2026 1915 1325 401 2303 2200 2125 1984 1392 477

Page 22: Pm 1.30 stefanick
Page 23: Pm 1.30 stefanick

Source: IMS Health NPA Plus

0

10

20

30

40

50

60

1995 1996 1997 1998 1999 2000 2001 2002 2003Annual Prescriptions by Formulation (millions)

Oral E Oral E/P Trnd/Vag

Annual Number of US Prescriptions for HT 1995 - Aug 2003

HERSWHIE+P WHI

E-only??

Hersh AL, Stefanick ML, Stafford RS JAMA 291: 2004; 291: 47-53

Page 24: Pm 1.30 stefanick

STOPPED - Increased StrokeNo CHD Benefit

Threshold Level

37% Increase Stroke(55% Increase Ischemic Stroke)

Risks Benefits

*Adapted from: Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333

Stopped 1.5 yrs early* had 0.3 more yrs of data

N.S. 37% Increase Pulmonary Emboli

47% increase DVTs

WHI E only Trial: Preliminary Findings, March 2004 (aver. 6.8 yrs)

Other Fractures

33% Decrease Hip Fracture

No Effect on CHD No Increase Breast Cancer

No Effect on Colorectal Cancer

Page 25: Pm 1.30 stefanick

Effects of CEE and Placebo on Disease Rates

0

1020

3040

5060

7080

90

StrokesBloodclots

HeartattacksColorectal

cancerDeaths BreastcancerHip

fractures

Number of cases per year

in 10,000 women

CEEPlacebo

WHI E-Alone (CEE) Trial: Absolute (annualized) Risk (6.8 Yrs*)*Preliminary Findings

The Women’s Health Initiative Steering Committee: JAMA 2004; 291: 1701-1712

Risk Benefit

P=.007 P=0.01P=.063 PE: ns6 DVTP=.03

12 6

Page 26: Pm 1.30 stefanick

Summary: WHI E+P* vs. E-Alone** Trialpublished: *July 2002 **April 2004

Concordant results Heart Disease – no benefit (for E+P, early harm) Strokes, Blood Clots – harmful Fractures – beneficial Dementia (if ≥ 65 yrs of age) – harmful *Brain MRI

Disparate Results Breast Cancer

Increased in E+P Trial (women with a uterus) Not increased in E-Alone Trial (women with prior hysterectomy)

Colorectal Cancer Decreased in E+P Trial (women with a uterus) No difference in E-Alone Trial

Global Index (Overall Risk/Benefit) Increased in E+P (CEE + MPA) Trial Neutral in E-Alone (CEE) Trial

Page 27: Pm 1.30 stefanick

WHI E-alone: CORONARY HEART DISEASE (CHD)Total and by Age (Rates per 10,000/year)

53 56

0

20

40

60

80

100

CHD

CEE only Placebo

N=10,739; 7.1 yrs follow-upHR= 0.95 (95%CI: 0.79-1.16)

1727

57 61

9686

0

20

40

60

80

100

50-59 60-69 70-79

CEE only Placebo

p = 0.07 for interaction

Hsia et al Arch Intern Med 2006; 166:357-365.

HR: 0.63(0.36-1.08)

HR: 0.94(0.71-1.24)

1.11(0.82-1.52)

Page 28: Pm 1.30 stefanick

Stefanick, et al Ann Epidemiol 2003; 13: S78-S86

36.6 35.227.7

0

10

20

30

40

50

50-59 60-69 70-79

BMI: 28.9 28.6 27.5

Mean BMI = 28.5 kg/m2

34.1% Obese (30.6% Normal Wt.)

WHI Hormone Trials: Percent Obese (BMI ≥30 kg/m2)

E+P Trial (Women with a Uterus)

PE

RC

EN

T O

F A

GE

GR

OU

P

51.045.8

34.1

010203040506070

50-59 60-69 70-79

Mean BMI = 30.1 kg/m2

44.6% Obese (20.7% Normal Wt.)

BMI: 31.2 30.2 28.6

E-Alone Trial (Hysterectomy)

Page 29: Pm 1.30 stefanick

Prior HT Use by Age at Baseline

0

10

20

30

40

50

60

70

80

Percentage

IntactUterus

Bilat Ooph No BilatOoph

50-59 y60-69 y70-79 y

Hysterectomy(36.5%) (56%)

CEE +MPA CEE only

Rossouw JAMA 2007;297:1465-1477

Page 30: Pm 1.30 stefanick

WHI E+P: Post-Intervention Follow-up

After E+P trial was stopped early (mean 5.6 yrs of intervention), WHI followed study participants through the planned termination of the trial (March 31, 2005)

Except for stopping the intervention and unmasking, the same trial protocol was followed, e.g. semi-annual monitoring to identify and classify study outcomes

Post-intervention information (July 8, 2002 to March 31, 2005) available on 15,730 (95% of eligible) participants:

mean of 2.4 years of post-trial follow-up

WHI has continued follow-up since 2005

Heiss et al, JAMA 2008; 299: 1036-1045

Page 31: Pm 1.30 stefanick

WHI E+P: Post-Intervention Follow-up

Cardiovascular risks disappeared CHD, Stroke*, Blood Clots – no longer increased

Fracture benefits disappeared Hip Fracture - no longer decreased

Cancer Breast Cancer - 27% (ns) more diagnosed post-Int. Colorectal Cancer - no longer decreased TOTAL CANCER - increased 1.24 (1.04-1.48)

Due to increase in variety of cancers, incl. Lung Cancer

All-cause Mortality -15% (ns) higher Most due to Cancer (E+P: 101 vs placebo: 69)

only 27 (E+P) and 16 (placebo) due to pre-specified CA

Heiss et al, JAMA 2008; 299: 1036-1045

Page 32: Pm 1.30 stefanick

Number of Prescriptions of Menopausal Hormone Therapy in U.S. by Year

N Engl J Med 2007; 356:16

Page 33: Pm 1.30 stefanick

Breast Cancer Incidence: Initiating (CT) or Using (OS), then Stopping, Menopausal Estrogen + Progestin in WHI

N Engl J Med 2009;360(6): 573-87Chlebowski et al (Stefanick)

WHI Observational Study (OS) Estrogen+Progestin Usersvs. Non-users - at Entry

Serial E+P Use

WHI Clinical Trial (CT)

Estrogen + Progestin vs.Placebo

Black Line = Sensitivity Analysis*

Intervention Phase HR =1.62 (1.02, 2.39)

Postintervention HR =1.26 (0.73, 2.20)

*censored 6 months after changing pills

During Intervention (Trial) After Stopping Study Pills HR = 1.26 (1.02, 1.53) HR = 1.27 (0.91, 1.72)

Page 34: Pm 1.30 stefanick

WHI E-only: Post-Intervention Follow-up

After E-only trial was stopped early (mean 7.1 yrs intervention), WHI continued to follow study participants through the planned termination of the trial (March 31, 2005)

By this time 54% of participants had stopped study medication. Median time on treatment: 5.9 or 5.8 years in active vs. placebo Median adherent time on treatment was 3.5 years

Postintervention follow-up: 47.2 (20.7) mo. ( thru August 14, 2099)

Consent obtained for annual mail and telephone follow-up for outcomes ascertainment in 78% of surviving eligible women 81% had at least 1 mammogram; 4.7% of active & 2.7% of placebo reported use of E alone after stopping

Intention-to-treat analysis, time-to-event methods

LaCroix, et al. JAMA 2011;305(13):1305-1314

Page 35: Pm 1.30 stefanick

Estrogen Alone Results All Participants by Intervention Period

Intervention Post-intervention Overall FU

CHD/Total MI 0 0 0

Stroke 0 0

DVT/PE 0

Breast cancer

Colorectal cancer 0 0 0

Hip fracture 0

All-cause mortality 0 0 0

Global index 0 0 0

LaCroix, et al. JAMA 2011;305(13):1305-1314

Page 36: Pm 1.30 stefanick

Estrogen Alone: Age Specific Results

50-59 years 60-69 years 70-79 years

CHD/Total MI 0

Stroke 0

DVT/PE 0 0

Breast cancer

Colorectal cancer 0 0

Hip fracture 0 0 0

All-cause mortality 0

Global index 0

LaCroix, et al. JAMA 2011;305(13):1305-1314

Page 37: Pm 1.30 stefanick

WHI E-only: Post-Intervention Follow-upCardiovascular: Stroke & VTE no longer elevated

CHD: aged 50-59baseline: HR 0.59 (0.38-0.90); age, pinteraction=0.05 MI: aged 50-59: HR 0.54 (0.34-0.86); 60-69,HR 1.05; 70-79,HR 1.23

age pinteraction=0.007 All CVD events: HR 1.06 (0.98-1.15)

Fracture: benefits disappeared

Cancer: Breast Cancer significantly lower in CEE (HR 0.77), all ages (Not high risk, e.g. family history, benign breast disease; Lancet Oncology, E March 2012)

Colorectal Cancer: women aged 70-79, 2-fold higher in CEE

All-cause Mortality AGE, p for interaction = 0.04 Women aged 50-59 @ baseline: HR 0.73 (0.53-1.00) No increase for women 60-69; slight increase for women 70-79

Global Index AGE, p for interaction = 0.009 aged 50-59: HR 0.85 (0.70-1.03) – possible benefit aged 70-79: HR 0.85 (1.01-1.32) – HARM

JAMA 2011;305):1305-1314

Page 38: Pm 1.30 stefanick

U.S. MHT Trends by Routes of Administration

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

Oral ET

Oral EPT

Vaginal

Transdermal

Intramuscular

WHI E aloneApril 2004

WHI E+PJune 2002

62%

76%

32%

58%

Tsai, Stefanick, Stafford. Menopause 2011; 18(4): 385-392

Page 39: Pm 1.30 stefanick

WHI Extension Study (ES) - 2005- 2010

Hormone27,347

Eligible:25,193

ES:20,425 (81.1%)

Diet48,836

Eligible: 45,560

ES: 37,844 (83.1%)

OS93,676

Eligible: 86,744

ES: 63,207 (72.9%)

Total WHI (CT + OS) = 161,809Eligible:150,075

Extension Study = 115,363 (77% of Eligible)Ages 57-91

CT

SHARe – Genome–wide Association Study (NHLBI): African-American & Hispanic PptsAdded rest of Hormone Trial Cohort, Core Biomarkers, e.g. lipids, glucose, creatinineCMS (Medicare) linkage, Medication Inventory

Page 40: Pm 1.30 stefanick

Hormone(82.9%)

Diet(86.2%)

OS (88.2%)

Total CT Eligible: 107,706consented: 93,544 (87%)

2010-15 Cohort Mean Age = 78 yrs

Regional Centers: Ongoing Outcomes Collection

In-Person Visit: 8000 women aged ≥72 yrs Ancillary Studies, e.g. WHIMS-Y, OPACH, NPAAS

WHI Physical Activity Trial Proposal

Baseline*Age Group

Number % of Eligible

50-54 14,470 91.2

55-59 21,527 90.7

60-69 43,352 87.1

70-79 14,195 77.4

*Baseline 60-79: 1993-1998nH White, 88% nH Black, 79% Hispanic, 77% Asian/PI, 83% Native American/Alaskan, 84%

WHI Extension 2010-2015

- currently working on a