Citations

Abstract Introduction: The appropriate assessment of HER2 amplification status is critical to determining which patients should receive HER2-directed therapy. An alternative to FISH is D-ISH (Ventana Medical Systems Tucson, Arizona) which utilizes chromogenic HER2 and chromosome 17 probes. Both FISH and D-ISH utilize formalin-fixed, paraffin-embedded (FFPE) human breast cancer tissue specimens. D-ISH has two principle advantages over FISH: it can be visualized using light microscopy and after analysis the specimens can be archived. Methods: We tested 250 samples with FISH and with D-ISH. Fifty specimens were controls: 25 cases with no HER2 or CEP17anomaly and 25 cases with HER2 amplification. There were also 200 test subjects of 50 cases each of chromosome 17 aneusomy, HER2 deletion (HER2/CEP17 ratio <0.8), HER2 duplication (HER2/CEP17 ratio 1.3–1.8), and equivocal results (HER2/CEP17 ratios between 1.8 and 2.2). FISH (Abbott Molecular) and D-ISH analysis were performed using methods described in the appropriate clinical kit package inserts, with the following exception: Four cases with CEP17 and HER2 co-amplification were also included and for FISH analysis these cases were reflexed to the use of chromosome 17 control probe (D17S122). Results: Four samples failed testing by D-ISH. There was a 63% (155/246) concordance between FISH and D-ISH by anomaly (aneusomy, duplication, deletion, etc.) and an 83% concordance by amplification status (non-amplified, equivocal, and amplified). D-ISH detected 18 (62%) of F-ISH-amplified cases. D-ISH resulted in lower estimates of HER2/CEP17 ratios than FISH, and many cases that were equivocal by FISH were normal by D-ISH. D-ISH did not detect HER2 amplification in any of the four HER2 and CEP17 co-amplified cases. Conclusions: We observed a lower concordance rate between FISH and D-ISH than the ∼95% rate in the D-ISH package insert. This lower concordance rate is likely a result of how this study was designed: it was biased toward common chromosome 17 anomalies and difficult specimens. Such specimens comprise about 60% of our current clinical HER2 biomarker practice. D-ISH may underestimate the HER2/CEP17 ratio, or FISH may overestimate this ratio. D-ISH also does not reliably detect HER2 amplification when the centromere of chromosome 17 is also co-amplifed. Compared to FISH, in this study cohort D-ISH had a significant false negative rate for the detection of HER2 amplification. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-05.

Abstract Background: Cognitive changes for older women who receive chemotherapy are poorly understood. Methods: Cancer and Leukemia Group B (CALGB) 49907 enrolled 633 women ≥65 years with early stage breast cancer and randomized them to standard adjuvant chemotherapy (AC or CMF) or capecitabine (N Eng J Med 360:2055, 2009). Patients enrolled on the Quality of Life companion study (N = 350) included women who had cognitive and psychological functioning sufficient for providing informed consent and participation in the trial (J Clin Oncol 29:1022, 2011). Participants completed an 18 item questionnaire focusing on their subjective report of cognitive function (attention, problem-solving, speed, new learning, and remote memory) at 6 time points (baseline, mid-treatment, within 1 month post treatment, and at 12, 18, and 24 months post treatment). Possible scores for each item ranged from 1–7 (‘above average’ - ‘severe problem’). Cognitive function score (CFS) was defined as the mean score of items 1–18. Cognitive impairment was defined as CFS 1.5 standard deviations above the overall average baseline. Univariate associations were tested between baseline CFS and patient characteristics (treatment, race, education, number of positive nodes, hormone receptor status, HER2 status, performance status, number of comorbidities, fatigue and depression) using Kruskal-Wallis testing. Frequency distributions were used to describe cognitive impairment. Multivariate analyses were not completed because few women reported subjective cognitive impairment during the study period. Results: 297 assessments were received at baseline, 280 at both mid-treatment and within 1 month post-treatment, 259 at 12 months, 245 at 18 months and 240 at 24 months post-treatment. The median age was 72 (65–85); 32% received AC, 21% CMF, and 47% capecitabine. Most women were white (87%) and had a performance status of 0 (73%). Approximately half of women had a high school degree or less and the majority had stage I-II (78%), hormone-receptor positive (68%) cancers and most did not experience depression or fatigue at baseline. At baseline, the overall mean CFS was 2.1 (‘normal ability’) and 19 women (6%) had mild to severe impairment. Baseline scores did not differ by treatment (p = 0.35). Worse cognitive function at baseline was associated with less education (p < 0.01), increased number of positive nodes (p = 0.02), 4+ comorbid conditions (p < 0.01) and fatigue (p = 0.02), although differences for these groups were small. During the study period, overall mean cognitive function scores remained at ‘normal ability’. At mid-treatment, within 1 month post treatment, 12, 18 and 24 months, cognitive impairment was present in 19 (6%), 19 (6%), 29 (10%), 31 (12%), 18 (7%), and 22 (9%), respectively. Conclusions: Our data suggest that in a healthy group of women without baseline cognitive impairments on objective screening, chemotherapy does not seem to be associated with changes in self-reported cognitive function over time. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-08-05.

Abstract Background: Age-related lobular involution (LI) is a physiological process, usually accelerated with menopause, in which the epithelial tissue of the breast gradually regresses. Our previous analysis of a cohort of more than 14,000 women who had a benign breast biopsy at the Mayo Clinic revealed that women who had undergone LI were at significantly reduced risk of subsequent breast cancer development. In our studies of postmenopausal women specifically, we found that more than 40% had not completed the process of LI, and that the increased breast cancer incidence in older women was strongly associated with incomplete LI. We sought to determine the potential protective mechanistic effects of lobular involution. Methods: We generated primary human mammary epithelial cell lines (HMECs) from breast biopsies of women who showed no LI (N = 6), partial LI (N = 7), or complete LI (N = 6). These cell lines were analyzed for proliferation in culture and profiled for genomic signatures using Affymetrix gene arrays. We also analyzed RNA isolated from a cohort of archived formalin-fixed, paraffin-embedded (FFPE) benign breast biopsy samples from postmenopausal women who had either completed the process of LI (N = 4) or who had not initiated LI (N = 8) for genomic signatures using Whole-Genome DASL Assays. Results: We found that LI was associated with decreased cellular proliferation and inhibition of processes associated with tumor development and progression. Specifically, we found that HMECs derived from benign breast biopsies in which LI was not evident showed increased proliferation and elevated expression of Twist (p = 0.002), a transcription factor associated with epithelial-mesenchymal transition (EMT) and breast cancer development. We are assessing differentially expressed genes for association with breast cancer risk using a nested case:control group of benign breast biopsies from women in our cohort who subsequently developed breast cancer (N = 85) vs those who did not (N = 142) and for whom LI status at the time of initial biopsy was known. Conclusions: LI may decrease cancer risk through inhibition of key tumorigenic processes. Identification of processes associated with the physiologic risk reduction seen with LI may provide insight into novel avenues for risk reduction. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-06-01.

Abstract Background: Our group and others have identified a subset of ER/PR(−) breast cancers characterized by expression of the androgen receptor (AR) and androgen-dependent growth (Doane 2006). We conducted a proof-of-concept multicenter phase II study to test the efficacy of the AR-antagonist, bicalutamide for the treatment of AR(+) ER/PR(−) MBC (NCT00468715). Results of the primary endpoint, clinical benefit rate (CBR), were presented at ASCO (Gucalp 2012). Data for the impact of bicalutamide on circulating hormone levels in women are limited. Elevations in serum testosterone (T) and estradiol (E) have been observed for men treated with bicalutamide. We hypothesized comparable patterns of change in circulating endocrine markers in response to bicalutamide for women with MBC. Methods: Patients (pts) with AR(+) (IHC ≥10%), ER/PR(−) (IHC <10%) MBC were eligible for treatment (tx) if ECOG performance status ≤2 and normal organ function regardless of menopausal status. There was no limit to prior tx except prior trastuzumab required if HER2(+). Tx consisted of bicalutamide 150mg orally daily in 28-day cycles (C). Toxicity assessed q4 weeks, response q12wks. Primary endpoint was CBR. Peripheral blood was collected for total and free T, E and sex hormone binding globulin (SHBG) at baseline, start of C2 (C2) and at end of study (EOS). Standard institutional assays were used. A Wilcoxon signed-rank test was done to compare baseline to C2 and EOS values. Results: 26 patients with AR(+) ER/PR(−) MBC were treated on study. Evaluable number (n) of pts at baseline, C2 and EOS are 26, 26 and 19 respectively. Two pts remain on study. Menopausal status: pre=2, post=24. Baseline median total and free T and estradiol were consistent with expected norms, however a wide range was observed (Table). There were no significant differences observed for median free T, total T, E or SHBG between baseline and C2 or baseline and EOS. Changes in hormone levels could not be stratified by menopausal status or response to bicalutamide given small sample size. Given the wide range of baseline values, we examined the percent change for each endocrine biomarker from baseline to C2 and EOS. As shown in the Table, there was no difference in median percent change observed across time points for each biomarker. Conclusions: No discernible patterns of change in T, E or SHBG were observed in response to bicalutamide therapy when given to women for the treatment of AR(+), ER/PR(−) MBC. These circulating hormones require further evaluation for use as a pharmacodynamic marker. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-02.

Abstract Background: A previous feasibility trial (E2104 – Ann Oncol 23(2):331–7,2012) suggested incorporation of B into anthracycline-containing adjuvant therapy was feasible but ongoing cardiac monitoring was required to define the true impact of B on cardiac function. Methods: Patients (pts) were assigned 1:2:2 to one of three treatment arms. In addition to doxorubicin and cyclophosphamide followed by weekly paclitaxel, patients received either placebo (Arm A – AC>T) or B during chemotherapy (Arm B - BAC>BT), or B during chemotherapy followed by B monotherapy (15 mg/kg q3wk) for an additional 10 cycles (Arm C – BAC>BT>B). Randomization was stratified and B dose adjusted for choice of AC schedule (classical q3wk − 15 mg/kg; dose dense(dd) q2 wk − 10 mg/kg). When indicated, radiation and hormonal therapy were administered concurrently with B (for Arm C pts). The primary cardiac endpoint was the incidence of clinically apparent cardiac dysfunction (CHF)defined as symptomatic decline in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN) or symptomatic diastolic dysfunction as assessed by independent review. Cumulative toxicity data as of Jan 23, 2012 are presented. Results: From 11.07 to 2.11, 4994 pts were enrolled. Median age was 52; 80% received ddAC. Chemotherapy associated toxicities including myelosuppression (Grade 4 neutropenia 16/20/19%) and neuropathy (Grade ≥ 3 8/8/8%) were similar across all arms. Grade ≥ 3 hypertension/thrombosis/proteinuria/hemorrhage was reported by 7/3/<1/<1% of B-treated pts. 99 pts developed CHF, most commonly reported at the post-AC or post-T evaluation. After a median follow-up of 26 months, the cumulative incidence of clinical CHF at 15 months from randomization in Arm A/B/C was 1.0/1.7/2.9% respectively. Median age of CHF pts was 57; median baseline LVEF of CHF pts was 60. Conclusion: Incorporation of B into anthracycline and taxane containing adjuvant therapy results in a significant but small increase in clinical CHF. The rate of clinical CHF is similar to that predicted by E2104 (2.5–2.9%) and reported In the FDA label for anthracycline pre-treated pts(3.8%). No unexpected toxicities were encountered. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-01.

Abstract PURPOSE: Hedgehog (HH) pathway has been implicated in maintenace and survival of breast cancer and cancer stem cells, EMT regulation, breast carcinogenesis and resistance to chemoradiation in solid tumors. Dysregulation of this pathway occurs in more than 50% of breast cancers. We have already demonstrated that immune-induced epithelial to mesenchymal transition (EMT) leads to the generation of breast cancer stem cells (BCSCs) from a parental epithelial breast cancer cell line in an in vivo murine model (Cancer Research 2009). The aim of our study is to demonstrate that resistance in the BCSCs is linked to HH hyperactivation and that the selective blockade of this pathway could eradicate this subpopulation of BCSCs in preclinical models. METHODS: One parental epithelial (E) and three mesenchymal BCSCs cell lines (M1, M2 and M3) were used for all the in vitro experiments. qRT-PCR was used to quantify the expression of the gene components of the pathway and gene targets. Measurement of Gli1, caspase 3 and Cyclin D1 protein expression was determined by Western blot. Cell viability assays were performed with Paclitaxel and the HH inhibitor GDC-0449. Apoptosis assays were performed when cell lines were treated with paclitaxel (10nM), GDC-0449 (25uM) or the combination of them. For the in vivo xenografted mouse model, 106 cells (E and M2) were inoculated sc respectively into the flank of 6–8 week-old syngeneic female FVB/N-TgN (MMTVneu) 202Mul/J mice. Treatment was started on daily GDC-0449 (ip), paclitaxel (ip on days 1, 4 and 8) or both drugs when tumors reached 0.5 cm2. Statistical analysis was performed using one-way ANOVA with the Bonferroni multiple comparison test. RESULTS: Activity of the HH measured by the expression of Gli1 was increased in BCSC cell lines as compared to E cell line (p < 0.001). This was antagonized as expected by treatment with GDC-0449. Reporter and expression assay showed that GDC-0449 decreases Gli1 transcriptional activity and levels of a HH downstream target gene, cyclin D1. In all BCSC lines (but not in the E cell line), a synergistic effect was showed with the combination treatment as compared to control (p ≤ 0.01) and to paclitaxel or GDC-0449 alone (p ≤ 0.05 respectively) as well as a highly increased apoptotic activity (p ≤ 0.001 with control and p ≤ 0.05 with monotherapy). Tumors derived from M2 injection regressed when the combination schedule was administered (p ≤ 0.05) at 2 weeks after the start of the treatment. CONCLUSION: The inhibition of the HH pathway with GDC-0449 plus paclitaxel demonstrates a synergistic therapeutic effect in comparison to monotherapy, as shown by increased apoptotic activity, cell cycle arrest and significant reduction of tumor size in vivo. Together these results provide the rationale for future clinical trials including the blockade HH and standard chemotherapy in order to eradicate the whole population of tumor cells (also BCSCs) within the tumors and avoid disease relapse and metastasis in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-07.

Abstract Background: Fibroadenoma (FA) is a relatively common benign breast tumor that can occur in women of any age, with a peak incidence during the second and third decades. The only previous study of this lesion reported that FAs are associated with a 2.2 times increased risk of developing invasive breast cancer (BC) compared to matched controls [1]. This relative risk may increase to 3.1 among patients with complex FA, and remains elevated for decades after diagnosis. However, this study did not thoroughly account for other forms of concomitant risk factors. Our investigative team sought to examine breast cancer risk among women with non-complex and complex FA, overall and stratified by other BC risk factors. Materials and Methods: The study cohort included women between ages 18 to 85 in the Mayo Benign Breast Disease (BBD) Cohort who underwent excisional breast biopsy between 1967and1991 and were found to have a FA. FA was defined histologically as a combination of epithelial and stromal proliferation. Complex FA was defined as FA associated with any of the following features: sclerosing adenosis, epithelial calcifications, papillary apocrine change, and microcysts greater than 3.0 mm. The primary endpoint was a diagnosis of BC, determined using the Mayo medical record and questionnaire information from study participants. A single breast pathologist, blinded to the initial diagnosis and clinical outcome, performed pathology review. Observed vs. expected BC risk across levels of FA was assessed via standardized incidence ratios (SIRs), using age-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) registry. Analyses were carried out overall and within subgroups of involution status (none, partial, complete) and overall histology (non-proliferative disease [NP], proliferative disease without atypia [PDWA] or atypical hyperplasia [AH]). Results: Of 9097 women in the Mayo BBD Cohort, FA were identified in 2139- non-complex in 1903 (20.9%) and complex in 236 (2.6%). The greatest proportion of FA occurred in the 40–69 age range. The mean ages for women with non-complex FA and complex FA were 45.7 and 50.2 years respectively. The SIR of breast cancer in the overall BBD cohort was 1.5 (95% CI [1.4–1.6]). The SIR among women with non-complex FA was 1.5 (95% CI [1.3–1.8]), and for complex FA increased to 2.41 (95% CI [1.7–3.4]). However, women with complex FA were more likely to have other concomitant high-risk histologic features such as PDWA and incomplete involution. In stratified analyses accounting for involution status and PDWA, complex FA did not demonstrate an independent increase in BC risk. Conclusion: Complex FA does not confer an increased risk for BC beyond other established histologic features. Therefore, women with complex FA should be managed based upon a risk level consistent with the major histologic category of PDWA and/or AH. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-08.

Abstract Background: Optimal early detection and prevention strategies for breast cancer are predicated on our ability to accurately identify women at increased risk for disease. Current breast cancer risk prediction models rely on clinical and epidemiologic features. As demonstrated with other cancers, such as those of the cervix and colon, cancer risk assessment is enhanced when the tissue at risk is examined for evidence of premalignant abnormalities. Here, we present a multivariate model for individualized breast cancer risk prediction that incorporates tissue features identified from biopsies from women with benign breast disease (BBD). Methods: We used our cohort of more than 9000 women diagnosed with BBD at the Mayo Clinic from 1967–1991, and identified a nested case:control series of 377 women who developed cancer (cases) matched with 734 women who did not (controls). We identified a set of variables that either alone or in two-way interactions contributed to a multivariable risk prediction model. We combined this relative risk model with the baseline incidence of breast cancer and the baseline hazard of death from our full BBD cohort to develop a risk prediction tool that computes absolute risk estimates for breast cancer. We calculated 5-year risk predictions for these cases and controls using our model and using the Gail model and compared c-statistics from these risk predictions. We validated our model using an independent set of 378 breast cancer cases and 728 matched controls drawn from our BBD cohort. Results: Cases and controls in the model development data set differed significantly on a number of features when examined individually. Those included in a multivariable relative risk model for breast cancer among women with BBD are shown below. After including interactions between lobular involution, and histologic impression, with age at first live birth/number of children, and degree of involution with sclerosing adenosis, we devised a model that predicts the absolute risk of breast cancer. Predicted five-year risks in the model development series, we observed a c-statistic of 0.66, higher than the c-statistic of 0.61 for the Gail model. With risk prediction estimates from our validation series of cases and matched controls, the c-statistic of our model decreased to 0.59 and the c-statistic for the Gail model was 0.55. Conclusion: We have identified an initial risk prediction model for breast cancer in women with BBD. The identified model includes basic demographic information as well as a number of histologic features of the tissue samples. Its initial performance is promising, providing improved discrimination over the Gail model in our replication data set. Further work is needed to identify features which might provide additional predictive information for breast cancer risk. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-03.

Abstract Background: ASP is hypothesized to decrease the risk of breast cancer (BRCA) and BRCA recurrences. Thus we performed an exploratory analysis of ASP and CC use within the NCIC CTG MA.27 adjuvant trial comparing exemestane (E;N=3789) to anastrozole (A; N=3787) with a factorial second randomization to CC or placebo (P). Neither A or E was superior in breast cancer outcomes. Baseline low-dose ASP use is an accepted surrogate of cardiovascular risk factors and was used as a stratification factor across all 4 arms. Randomization to CC-P was discontinued after 18 months (n = 1622) due to concerns of cardiac toxicity. Methods: Patients taking >81mg of ASP daily at baseline were ineligible for randomization and use of >81mg of ASP daily was not allowed. Women enrolled during CC randomization were included in the comparison of E and A, stratified by whether they had been randomized to CC [yes, no;N=1622] and concomitant low-dose ASP [≤81 mg/day (yes, no); N=2209]. Other stratification factors included: lymph-nodes (negative, positive, or unknown); prior adjuvant chemotherapy (yes, no). The primary endpoint, event-free-survival (EFS), was defined as time from randomization to time of locoregional or distant disease recurrence, new primary breast cancer, or death from any cause. Secondary endpoints included overall survival (OS) defined as time from randomization to time of death from any cause and distant disease-free-survival (DDFS), defined as time from randomization to time of distant disease recurrence. Univariate (uni) assessment of CC and ASP use was assessed with stratified log-rank test, adjusting for lymph-node status and adjuvant chemotherapy and applied by intention-to-treat. Exploratory multivariate (multi) analyses (N = 1622) had forced inclusion of treatment and used step-wise forward stratified Cox modeling to examine the effects of CC, ASP use and baseline patient characteristics on outcomes; a factor was added with Wald test statistic p ≤ 0.05. Results: At median follow-up of 4.1 years, 186/1622 (11%) patients had an EFS event; 125 (8%) had died from any cause, and 80 (5%) had distant BRCA relapse. CC did not have significant uni association with outcomes: EFS p-value=0.92; OS p-value p = 0.56; DDFS p-value=0.55. ASP use was associated with worse EFS [p = 0.006, HR 1.48 (95% CI 1.12–1.96)], worse OS [p = 0.0002, HR 1.87 (95% CI (1.35–2.61)], and non-significant difference in DDFS (p = 0.72). CC had no multi association with EFS, OS or DDFS. ASP use had no multi association with EFS and DDFS (p > 0.05). However, ASP use had multi prognostic association with worse OS [p = 0.01; HR 1.67 (95% CI 1.13–2.49)]. Conclusions: Users of either CC or low dose ASP had similar DDFS to non-users in MA.27. As expected, low-dose ASP users (with presumptive cardiovascular risk factors) had worse OS than non-users. Inadequate numbers of patients randomized to CC and lack of randomization to aspirin leaves inadequate evidence from MA.27 to determine whether anti-inflammatories influence breast cancer outcomes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-02.

Abstract Background: It has long been known that chemotherapy can result in premature menopause, causing follicular senescence and estrogen depletion with associated hot flashes and mood alterations. What is less well appreciated is whether the stroma of the ovary is equally impacted after chemotherapy, resulting in androgen deprivation. The aim of this pilot study was to evaluate whether androgen levels are adversely affected after chemotherapy and whether this is associated with unwanted symptoms. Methods: Women who were premenopausal, newly diagnosed with breast cancer, and about to undergo adjuvant chemotherapy were followed longitudinally. Women with adrenal insufficiencies, taking steroids, oral contraceptives, or had had previous chemotherapy were excluded. Self report questionnaires regarding sexual function, fatigue, mood, menstrual symptoms; menstrual diaries; and blood were collected at 4 points: before treatment, mid chemotherapy, post chemotherapy and 6 months later. Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) (adrenal hormone), bioavailable testosterone (bioT), androstenedione (Adione) (stromal hormone), estrone (E1), estradiol (E2) (follicular hormone), sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH) were evaluated. Descriptive statistics, comparisons of means by two sided t-tests and Pearson correlation coefficients were computed. Six month post treatment data are reported. Results: 24 women were accrued and 21 provided serum and questionnaires through 6 months. All sex steroid hormones decreased during chemotherapy and did not return to baseline by 6 months for the group as a whole. At 6 months, 14 women were postmenopausal per FSH, E2 and menstrual diaries and 7 had resumed menses. There were no significant differences in hormone concentrations at baseline between women who ended up menopausal from those who resumed menses. However, at 6 months, postmenopausal women had significantly lower concentrations than premenopausal women of E2 (289 pg/ml pre- 9 pg/ml post), E1 (132 pg/ml pre- 22 pg/ml post), and Adione (102 ng/dL pre- 56 ng/dL post), but not DHEA-S or bioT (all p < .01). E2 was significantly correlated with Adione (R = .47 p = .03), and E1 (R = .57, p = .007). Low to moderate correlations were found between hormone concentrations and symptoms. The use of tamoxifen was significantly, and negatively correlated with the total score on the Female Sexual Function Index (r = −.572, p = .005), indicating worse sexual function for women on tamoxifen. Conclusion: These data support the hypothesis that the post chemotherapy ovary suffers both follicular and stromal dysfunction, as noted by lower Adione, which is specific to the ovarian stroma. Adione concentrations in the postmenopausal group women are similar to published reports of women post oophorectomy. This is the first longitudinal study we are aware of to evaluate ovarian stromal function in women undergoing chemotherapy. This total hormone depletion may be why women experiencing chemotherapy induced menopause report severe and distressing menopausal symptoms such as hot flashes. Estrogen is often implicated, but androgen deprivation in this population should be taken into consideration when planning interventions to improve health related quality of life. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-01.