Breast Cancer Survivorship Michelle Melisko MD Assistant Clinical Professor UCSF Breast Care Center
Survivors Who are they? An estimated 210,000 women were diagnosed with breast cancer in the year 2007 Many of these women will be rendered free of cancer, but will need ongoing disease specific care and surveillance The estimated number of breast cancer survivors in the year 2003 was 2.3 million
Survivorship Issues What is the impact on health of being a longterm cancer survivor? What is the cost of being a survivor physically, emotionally, spiritually and financially? Is our healthcare system prepared to handle the growing number of people diagnosed with cancer, and the treatment and follow up needed for quality of life?
Differences in breast cancer follow up care - A world perspective In many countries, access to subspecialists is limited Primary care physicians and other physician extenders play a bigger role in health care in general
GREAT BRITAIN In a randomized trial of 296 women with a history of breast cancer, transfer of routine oncology follow-up care to a family physician did not result in an increase in the time to diagnosis of recurrence Patient satisfaction was greater Health service costs were less Anxiety and health related quality of life were unaffected
CANADA 968 early-stage breast cancer patients who had completed adjuvant treatment were randomized to follow up in a cancer center or with their own family physician No differences in number of recurrences, deaths, recurrence related serious clinical events No difference in patient reported healthrelated quality of life Breast cancer follow up care is routinely provided by primary care MDs in UK and Canada
SWEDEN A study compared nurse-led follow-up vs. physician follow-up in 264 women with newly diagnosed Stage I or II breast cancer Patients completed QOL and satisfaction questionnaires at baseline and twice a year for 5 years There were no differences between the groups concerning time to recurrence or death Ratings of Hospital Anxiety and Depression Scale (HADS), and Satisfaction and Accessibility (SaaC) scales did not show any differences between the groups Levels of anxiety and depression were generally low and patient satisfaction was high This study supports that follow-up care with an experienced nurse professional is safe and effective
What do breast cancer survivors need? Comprehensive follow-up care Appropriate breast imaging and examination Symptom management, spiritual and emotional support Resources financial, emotional, informative and supportive More information about adopting and maintaining healthy lifestyles More research about the effects of treatment
Breast Cancer Follow Up: What to do and What NOT to do American Society of Clinical Oncology 2006 Update of the Breast Cancer Follow-Up and Management Guidelines in the Adjuvant Setting (JCO Nov 1 2006: 5091-5097) Routine labs, CT scans, bone scans not necessary or indicated American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast (JCO Nov 20 2007: 5287-5312) TUMOR MARKERS ARE NOT RECOMMENDED
Breast Imaging Recommendations NCCN, ACSO, and ACS guidelines recommend follow up mammograms every 6-12 months for affected breast in the setting of breast conserving surgery Breast MRI only indicated for the following: Pts with equivocal mammographic and/or PE findings Pts presenting with malignant axillary adenopathy and unknown site of primary tumor Patient with extensive or locally advanced cancer undergoing chemotherapy Screening of women at increased ( 20% to 25%) lifetime risk Known BRCA1 or BRCA2 gene mutation carrier Pt with first-degree relative with a BRCA1 or BRCA2 gene mutation who has not had genetic testing themself Radiation therapy to the chest between the ages of 10-30 yo Genetic disease such as Li-Fraumeni or Cowden syndrome or one of these syndromes in first-degree relatives Orel S, JCO Feb 2008
The spectrum of breast cancer treatments and possible complications 1. Surgery (Lumpectomy, mastectomy, SLND, full, ALND, reconstruction) 2. Chemotherapy 3. Radiation 4. Hormonal therapy (Aromatase Inhibitors and/or Tamoxifen) 5. Trastuzumab 1. Breast/chest wall pain, lymphedema 2. Cardiac issues/chf (only with anthracyclines, very rare), neuropathy (taxanes), premature menopause, leukemia (very rare) 3. Radiation pneumonitis, brachial plexopathy, scarring/fibrosis of breast tissue, angiosarcoma (very rare) 4. Hot flashes, mood swings, weight gain, vaginal symptoms, joint pains 5. Cardiac issues/chf (Rare)
What medications breast cancer patients might be taking And what to worry about with these medications
Tamoxifen Tamoxifen has been shown to decrease disease recurrence and increase overall survival Remains the standard of care for pre-menopausal breast cancer patients Tamoxifen use has been associated with endometrial cancer and thromboembolism CYP2D6 pharmacogenetics varies and results in different levels of therapeutic efficacy EBCTG. Lancet.. 1998;351:1451-1467 1467 (A); Johnston et al. Nat Rev Cancer. 2003;3:821-831(B); 831(B); Knox et al. Presented at: American Society of Clinical Oncology Annual Meeting; June 2-6, 2 2006; Atlanta, Ga (A).
The Evolving Role of Adjuvant Hormonal Therapy AIs have been shown to decrease disease recurrence compared with tamoxifen Several regimens have been shown to be more effective than 5 years of tamoxifen alone 5 years of adjuvant AI therapy 2 to 3 years of tamoxifen, followed by 2 to 3 years of an AI 5 years of tamoxifen, followed by 5 years of AI Winer et al. J Clin Oncol. 2005;23:619-629 629 (A).
Adjuvant Hormonal Therapy Trial Designs Direct Comparison Switching Extended Adjuvant Supporting Trials ATAC BIG 1-981 Supporting Trials IES ITA ARNO/ABCSG Supporting Trials MA-17 Sequencing Supporting Trials BIG 1-981 (not yet reported) Upfront vs Switching Supporting Trials TEAM (not yet reported) Baseline Year 5 Year 10 Study population Tamoxifen AI Placebo ATAC Trialists Group. Lancet.. 2002;359:2131-2139 2139 (A); The Breast International Group (BIG) 1-981 Collaborative Group. N Engl J Med.. 2005;353:2747-2757 2757 (A); Coombes et al. N Engl J Med.. 2004;350:1081-1092 1092 (A); Jakesz et al. Lancet.. 2005;366:455-462 462 (A); Boccardo et al. J Clin Oncol.. 2005;23:5138-5147 5147 (A); Goss et al. J Natl Cancer Inst.. 2005;97:1262-1271 1271 (A).
ATAC Trial Design Phase 3, Randomized, Double-Blind Trial Postmenopausal women Early breast cancer (N=9366) RANDOMIZATION 5 years of anastrozole (n=3125) 5 years of tamoxifen (n=3116) 5 Years Total Therapy 5 years of tamoxifen + anastrozole* (n=3125) *Combination arm was closed because of low efficacy. ATAC Trialists Group. Lancet.. 2002;359:2131-2139 2139 (A); ATAC Trialists Group. Cancer. 2003;98:1802-1810 1810 (A); ATAC Trialists Group. Lancet.. 2005;365:60-62 62 (A).
Adverse Events Number of Patients (%) ATAC Anastrozole Tamoxifen Odds Ratio, (n=3092) (n=3094) A vs T (95% CI) P Value Hot flushes 1104 1264 (40.9%) <.0001 Arthralgias (35.7%) 911 (29.4%) <.0001 Vaginal bleeding 1100 317 (10.2%) <.0001 (35.6%) Endometrial* 17 (0.8%).02 167 (5.4%) Fractures 237 (7.7%) <.0001 5 (0.2%) Hip 31 (1.0%).5 340 Spine (11.0%) 27 (0.9%).03 Wrist/Colles 37 (1.2%) 63 (2.0%).4 All other sites 45 (1.5%) 142 (4.6%) <.0001 Venous 72 (2.3%) 140 (4.5%) 0.0 0.5 1.0 1.5 2.0 2.5 3.0.0004 thromboembolic events *Excluding patients with hysterectomy 220 (7.1%) at baseline, recorded at any time; patients with 1 or more fractures occurring at any time before recurrence (includes patients no longer receiving treatment); patients may have had 1 or more fractures at different sites. 87 (2.8%) ATAC Trialists Group. Lancet. 2005;365:60-62 62 (A).
Change in BMD Over 5 Years ATAC Anastrozole Tamoxifen 4 Lumbar Spine (P<.0001*)( Total Hip (P<.0001*)( Change From Baseline (%) 2 0-2 -4-6 -8 Year 1 Year 2 Year 5 Year 1 Year 2 Year 5 *In favor of tamoxifen. Coleman. Presented at: the American Society of Clinical Oncology Annual Meeting; June 2-6, 2006; Atlanta, Ga (A).
BIG 1-98 Trial Design Phase 3, Randomized, Double-Blind Trial Postmenopausal women Early HR+ breast cancer (N=8010) RANDOMIZATION 5 years of tamoxifen 2 years of tamoxifen 3 years of letrozole 2 years of letrozole 3 years of tamoxifen 5 Years Total Therapy 5 years of letrozole The Breast International Group (BIG) 1-981 Collaborative Group. N Engl J Med.. 2005;353:2747-2757 (A).
Letrozole Increases DFS 100 BIG 1-98 Letrozole* (351 events) DFS (%) 75 0 P=.003 Tamoxifen* (428 events) 0 1 2 3 4 5 Years After Randomization Letrozole No. at risk 4003 3892 2964 1261 892 567 DFS (%) 97.7 95.1 90.5 86.8 84.0 Tamoxifen No. at risk 4007 3896 2926 1238 866 544 DFS (%) 97.6 93.4 89.0 84.6 81.4 *Data comparing both monotherapy and sequential therapy arm. Events and follow-up in the sequential group that occurred 30 days after switch were included. d. The Breast International Group (BIG) 1-981 Collaborative Group. N Engl J Med.. 2005;353:2747-2757 (A).
Safety Profile BIG 1-98 Letrozole (n=3975) Tamoxifen (n=3988) P Value Thromboembolic events 61 (1.5%) 140 (3.5%) <.001 Vaginal bleeding 132 (3.3%) 263 (6.6%) <.001 Hot flushes 1332 (33.5%) 1516 (38.0%) <.001 Night sweats 554 (13.9%) 647 (16.2%).004 Fractures 225 (5.7%) 159 (4.0%) <.001 Arthralgias 806 (20.3%) 491 (12.3%) <.001 Hypercholesterolemia 1733 (43.6%) 766 (19.2%) NR The Breast International Group (BIG) 1-981 Collaborative Group. N Engl J Med. 2005;353:2747-2757 2757 (A).
Breast Cancer Survivorship Issues for Oncologist and Primary Care Physicians Bone Density Loss Arthralgias Hot Flashes Vaginal Dryness / Decreased Libido
Bone Mineral Density
Aromatase Inhibitors and Bone Loss AI-induced estrogen ablation accelerates bone loss and augments fracture risk in postmenopausal women AI-induced bone loss more rapid than bone loss associated with postmenopausal status alone IV bisphosphonates may decrease AI-associated bone loss Z-FAST study evaluated 36-month safety and efficacy of upfront vs delayed IV ZA in decreasing AI-associated bone loss in postmenopausal women with early breast cancer Brufsky A, et al. SABCS 2007. Abstract 27.
Z-FAST: Upfront vs Delayed ZA Postmenopausal women with ER-positive or PgR-positive breast cancer (N = 602) Upfront ZA* 4 mg IV every 6 months + Letrozole 2.5 mg/day (n = 301) Delayed ZA* + Letrozole 2.5 mg/day (n = 301) *All patients treated with calcium and vitamin D. ZA initiated when T-score decreased to < -2 or clinical fracture occurs. Brufsky A, et al. SABCS 2007. Abstract 27.
Z-FAST: Change in BMD for Delayed vs Upfront ZA Change in BMD at 36 Mos (%) 4 3 2 1 0-1 -2-3 -4 P <.0001 Lumbar Spine BMD Brufsky A, et al. SABCS 2007. Abstract 27. Upfront ZA Delayed ZA P <.0001 Total Hip BMD Lumbar spine and total hip BMD increased for patients on upfront ZA but decreased for patients on delayed ZA By 36 months, 62 (21%) patients in the delayed arm initiated ZA Trend toward less disease recurrence in upfront arm vs delayed arm 9 (3.5%) vs 16 (6.9%), respectively (P =.13)
Fracture Rates at 36 months No. of Patients (%) Type of Fracture Clinical Significant trauma Minimal or no trauma Asymptomatic Other Radiological spine Upfront Group (n=300) 11 (3.7) 2 (0.7) 2 (0.7) 1 (0.3) 1 (0.3) Delayed Group (n=300) 12 (4.0) 3 (1.0) 1 (0.3) 2 (0.7) 1 (0.3) Total 17 (5.7) 19 (6.3)
Additional Adverse Events Renal disorders Grade 1-2 renal insufficiency Upfront group, 2 patients Delayed group, 0 patients Both suspected to be related to zoledronic acid Atrial fibrillation Grade 1-2 Upfront group: 3 patients Delayed group: 0 patients Grade 3-4 Upfront group: 4 patients Delayed group: 4 patients None suspected to be related to study drugs Osteonecrosis of the jaw No confirmed cases
Conclusions Upfront administration of zoledronic acid (4 mg IV every 6 months) was effective in preventing bone loss in postmenopausal women on AI therapy at 36 months of follow-up Increased lumbar spine and total hip bone mineral density Bone-specific alkaline phosphatase and serum NTX were effectively suppressed No differences were seen in symptomatic or asymptomatic fracture rates at 36 months with upfront therapy Zoledronic acid was safe and well tolerated Identifying high risk patients is critical to determine who should receive upfront therapy: Not everyone needs it!
Arthralgias
ATAC Substudy: Joint Symptoms With Anastrozole vs Tamoxifen Joint problems secondary to estrogen depletion is well documented after menopause and known adverse effect of AI use Joint symptoms* analyzed in 2799 and 2795 patients on anastrozole and tamoxifen from ATAC trial at 5 years Occurred in 1128 (36.5%) vs 957 (30.9%) patients (OR: 1.28 [95% CI: 1.15-1.43; P <.001]) Most joint symptoms mild to moderate Occurred soon after treatment initiation Symptoms abated in both arms with time on treatment *Joint symptoms (occurring during treatment or within 14 days of cessation) defined as arthralgias, arthritis, arthrosis, or other joint disorder. Sestak I, et al. SABCS 2007. Abstract 2071.
ATAC Substudy: Risk Factors for Developing Joint Symptoms Risk Factor Joint Symptoms, n (%) Multivariate OR (95% CI) P Value Anastrozole 1040 (37.2) 1.31 (1.16-1.47) <.001 Previous HRT 840 (42.3) 1.52 (1.35-1.72) <.001 Chemotherapy 485 (38.9) 1.20 (1.04-1.38).01 HR negative 130 (27.7) 0.76 (0.61-0.85).02 Region of origin (vs rest of world) UK 563 (30.2) 1.19 (1.01-1.37).04 North America 803 (47.7) 2.1 (1.81-2.43) <.001 BMI > 30 kg/m 2 (vs < 25) 555 (39.3) 1.36 (1.17-1.57) <.001 Use of previous HRT led to greater difference in joint symptoms between patients on anastrozole vs tamoxifen Sestak I, et al. SABCS 2007. Abstract 2071.
Joint Problems Observed in Patients Receiving AIs and Tamoxifen 101 women received Let followed by Anast or Anast followed by Let immediately after surgery for 6 mos 76 women received extended adjuvant Let followed by Anast or Anast followed by Let after 5 years of tamoxifen No difference in incidence of joint pain between anastrozole vs letrozole, but fewer joint symptoms with tamoxifen vs AIs Tamoxifen vs anastrozole (P =.0126) Tamoxifen vs letrozole (P =.0192) Renshaw L, et al. SABCS 2007. Abstract 2072. Drug, n (%) Letrozole but not anastrozole Anastrozole but not letrozole Tamoxifen but not letrozole Tamoxifen but not anastrozole Letrozole but not tamoxifen Anastrozole but not tamoxifen Joint Symptoms on One Drug But Not Another 83 (56) 83 (55) 23 (57) 23 (74) 38 (74) 41 (85)
Hot Flashes
% Reduction (Mean) 100 80 60 40 20 Mean Hot Flash Score Reduction Randomized Studies Black Cohosh (n=58) Placebo (n=420) Soy (n=78) Vitamin E (n=53) Clonidine (n=75) Fluoxetine (n=36) Ven (vs MPA) (n=94) Venlafaxine (n=48) MPA 400 mg (n=94) Megestrol (n=74) 0 0 1 2 3 4 5 6 Week
Newer Antidepressants for Hot Flashes Published Manuscripts with Baseline Week Data Agent Author Publication Venlafaxine Loprinzi et al Lancet, 2000 Fluoxetine Loprinzi et al JCO, 2002 Paroxetine Stearns et al JAMA 2003 Stearns et al JCO 2005 Sertraline Kimmick et al The Breast Journal, 2006 Gordon et al Menopause 2007 Grady et al Obstet Gynecol 2007
Venlafaxine for Hot Flashes Double-blind, placebo-controlled, randomized trial of 4 weeks treatment Placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54) All venlafaxine treatment started at 37.5 mg daily and increased in the 75 mg and 150 mg groups Primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity) based on daily pt diaries After week 4 of treatment, median hot flash scores were reduced from baseline by 27%, 37%, 61%, and 61% in the four groups Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group Loprinzi et al, 2000
Study Results 100 Hot flash score (percent of baseline) 80 60 40 20 Placebo Venlafaxine 37.5 mg/d Venlafaxine 150 mg/d Venlafaxine 75 mg/d 0 Baseline 1 2 3 4 5 6 Weeks Loprinzi et al, Lancet 2000
Fluoxetine for Hot Flashes Double-blinded, randomized, two-period (4 weeks per period) cross-over trial The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score 81 randomized women began protocol therapy By the end of the first treatment period, hot flash scores (frequency x average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P =.02) The fluoxetine was well tolerated Loprinzi et al, 2002
Study Results Hot flash score (percent of baseline) 100 80 60 40 20 Placebo Fluoxetine 20 mg/d 0 Baseline 1 2 3 4 5 6 Weeks Loprinzi et al, JCO 2002
Paroxetine and Hot Flashes Women who had at least two hot flashes a day for >1 month were eligible 151 women were assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 wks, or placebo for 4 wks followed by paroxetine 10 mg or 20 mg for 4 wks Participants completed baseline daily hot flash diaries for one wk prior to and throughout the study, and QOL questionnaires at baseline, wk 5 and wk 9 Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo Women were less likely to discontinue low-dose paroxetine Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P =.01).
Study Results Hot flash score (percent of baseline) 100 80 60 40 20 Placebo Placebo Paroxetine 10 mg/d Paroxetine 20 mg/d 0 Baseline 1 2 3 4 5 6 Weeks Stearns et al, JCO 2005
Gabapentin and Hot Flashes Randomized, double-blind, placebo-controlled trial to assess the efficacy of gabapentin for hot flashes in women with breast cancer 420 women with breast cancer were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day Patients kept a diary on the frequency, severity, and duration of hot flashes 1 wk before and during wks 4 and 8 of treatment Percentage decreases in hot-flash severity score between baseline and wks 4 and 8, respectively were: 21% and 15% in the placebo group; 33% and 31% in the group assigned gabapentin 300 mg; and 49% and 46% in the group assigned gabapentin 900 mg The differences between the groups were significant (p=0.0001 at 4 wks and p=0.007 at 8 wks by ANCOVA for overall treatment effect Only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity Pandya KJ et al. Lancet 2005;366:818 824
Change from baseline in hot flash severity 0-2 -4 Hot Flash Severity -6-8 -10 Placebo Gabapentin 300 mg Gabapentin 900 mg -12-14 Baseline Week 4 Week 8 Pandya KJ et al. Lancet 2005;366:818 824.
Sexual Dysfunction after Breast Cancer Vaginal Dryness and Decreased Libido
Testosterone and Libido Studies that have looked at correlations between testosterone and libido have not been conclusive No definitive research has been completed in women with a diagnosis of cancer
Transdermal Testosterone in Female Cancer Survivors with Decreased Libido NCCTG N02C3 4 weeks Testosterone* 10 mg/day 4 weeks Placebo** R Placebo** Testosterone* 10 mg/day *In Vanicream ** Vanicream JCO 24:469S, 2006 ASCO abstract #8507
Libido Change from Baseline 9 8 7 6 5 4 3 2 1 0 1st Period P=0.58 2nd Period P=0.71 placebo testosterone
Mean Change from baseline: T e s t o s t e r o n e ng/dl Free testosterone concentrations 2 1 0-1 1st period 2nd Period placebo testosterone P<.0001 (Norms: 0.3-1.9 ng/dl)
Vaginal Dryness Non-estrogenic vaginal lubricants Vaginal estrogen Pilocarpine Vaginal Testosterone Cream
Placebo Replens Replens Placebo Loprinzi et al JCO 15, 969-973; 1997
Vaginal estrogens compared to Replens for vaginal dryness Open-label study comparing effects of Replens to a local estrogen therapy in the treatment of vaginal dryness symptoms 15 women evaluated in each treatment group during a 12-week period Replens was safe and effective alternative to estrogen vaginal cream Both therapies exhibited statistically significant increases in vaginal moisture, vaginal fluid volume, and vaginal elasticity with a return of the premenopausal ph state Nachtigall LE, Fert Steril 1994
Vaginal estrogen may be better than Replens for vaginal dryness?? 39 pt study compared Replens to Dienoestrol (Cilag), an estrogenic vaginal cream Replens was given 3x/wk during 12 wks of the study, while Dienoestrol was administered daily during the first 2 wks and then 3x/wk Vaginal dryness index, itching, irritation, dyspareunia, ph and safety were evaluated every week the first month and every month thereafter Both treatments had a significant increase on vaginal dryness index Hormonal compound was significantly better than Replens Itching, irritation and dyspareunia significantly decreased or disappeared with no difference between the treatments Bygdeman M, Swahn ML, Maturitas 1996.
Are vaginal estrogens safe in breast cancer patients? The jury is still out
Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors Serum estradiol, FSH, and LH levels were followed in 7 postmenopausal women using vaginal estrogen preparations while on AIs for breast cancer Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women Vagifem significantly raised estradiol levels, at least in the short term This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated Kendall et al, Annals Oncol 2006
Phase III Trial of Pilocarpine in Patients with Sjögren s Syndrome Main outcome related to oral and ocular dryness. A statistically significant decrease in vaginal dryness was also reported (p=0.02, 25% versus 14% reduction). Vivino et al. Arch Intern Med 159(2):174-81, 1999.
Oral pilocarpine to treat vaginal xerosis associated with chemotherapy-induced amenorrhea in pre-menopausal women Pilocarpine (5mg qid) for premenopausal women who had developed vaginal dryness after receiving cyclophosphamide Authors reported that all four of these participants experienced a marked clinical improvement in vaginal dryness Le Veque FG, Hendrix S. J Clin Oncol (ASCO Annual Meeting Proceedings, Abstract 8099); 22(14S):749, 2004.
Proposed Study Vaginal dryness Pilocarpine 5 mg QID Pilocarpine 5 mg BID Placebo BID or QID
Efficacy and Safety of Vaginal Testosterone for Atrophic Vaginitis in Breast Cancer Patients on AIs: a Pilot Study Objective: Determine the efficacy and safety of topical testosterone in this patient population in patients with AI-related atrophic vaginitis. Results: Six postmenopausal patients taking AIs for early breast cancer who had symptoms of atrophic vaginitis were given vaginal testosterone 300 µg daily for 28 days. Estradiol levels remained low, and testosterone level changes were small after treatment. Self-reported symptom scores (0 = none, 3 = severe) improved for 5 women: Vaginal dryness (2.5 pretreatment to 0.5 posttreatment) Dyspareunia (2.2 pretreatment to 0.83 posttreatment) Itching/irritation (1.0 pretreatment to 0.83 posttreatment) Average vaginal ph decreased from 4.83 to 4.5. Safety: 1 patient with vaginal rash and 1 patient with headache and pruritis Witherby, SABCS 2007, Abstract 6086
UCSF Trial - A Phase II Study of Vaginal Testosterone Cream vs. the ESTRING for Vaginal Dryness or Decreased Libido in Early Breast Cancer Patients Treated with AIs Objectives: To evaluate the safety, based on serial estradiol levels, of intravaginal testosterone cream or the ESTRING administered for relief of vaginal dryness and/or decreased libido related to AI therapy in early breast cancer patients To document the systemic estradiol and testosterone levels in early breast cancer patients on AIs being treated with intravaginal testosterone cream or the ESTRING
Major Inclusion Criteria Stage I-III breast cancer on adjuvant AI Must have started AI at least 60 days prior to enrolling Postmenopausal status No period for >12 months If patient has been rendered post-menopausal by adjuvant chemotherapy but has had a period within the past 12 months, post-menopausal levels of serum estradiol must be documented on two lab tests at least 3 months apart
Major Exclusion criteria History of radiation to the vaginal area Concurrent treatment with any type of oral, injectable or topical form of estrogen or androgen therapy Initiation of topical moisturizers or herbal or alternative medicines for vaginal dryness Use of vaginal hormonal products (rings, inserts, creams, gels) containing estrogens or androgens within the past 30 days History of sexual dysfunction prior to diagnosis of breast cancer
TREATMENT / EVALUATION Patients will be randomized to a 12 week course of either: Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment OR Estring 2mg ring inserted vaginally once every 12 weeks Serum estradiol at baseline, week 4 and week 12 Serum testosterone at baseline, week 4 and week 12 in testosterone cream arm Repeat estradiol at week 6-8 if week 4 estradiol is elevated outside post-menopausal range or >10pg/ml above baseline
Takeaway Messages Breast cancer patients face many long term complications and symptoms from their treatment Many breast cancer patients will be cured of their disease Not every symptom is a recurrence of breast cancer!! Before you order a scan or test, consider contacting patient s treating oncologist whenever possible to discuss what test would be best and what the implications will be