Ruth Oratz, M.D.

Physician survey of the effect of the 21-gene recurrence score assay results on treatment recommendations for patients with lymph node-positive, estrogen receptor-positive breast cancer
Oratz, Ruth; Kim, Benjamin; Chao, Calvin; Skrzypczak, Stanley; Ory, Caron; Bugarini, Roberto; Broder, Michael
2011 Mar;7(2):94-99, Journal of Oncology Practice
PURPOSE: To survey the effect of the 21-gene recurrence score (RS) assay results on adjuvant treatment recommendations for patients with lymph node-positive (N+), estrogen receptor-positive (ER+) breast cancer. METHODS: Medical oncologists who ordered the 21-gene RS assay were invited to complete a survey regarding their most recent patient with N+/ER+ breast cancer. We obtained responses from 160 (16%) of the 1,017 medical oncologists. RESULTS: Most of the respondents were in community (71%) versus academic (25%) settings and had practiced for a median of 11 years. T1, T2, or T3 disease was reported in 62%, 35%, and 3% of patients, respectively. One, two, three, or >/= 4 nodes were reported in 69%, 18%, 6%, and 3% of patients, respectively. Eighty-six percent of the oncologists made treatment recommendations before obtaining the RS; 51% changed their recommendations after receiving the RS. In 33%, treatment intensity decreased from chemotherapy plus hormonal therapy to hormonal therapy alone. In 9%, treatment intensity increased from hormonal therapy alone to chemotherapy plus hormonal therapy. In 8%, treatment recommendations changed in a way that did not fit the definition of either increased or decreased intensity. CONCLUSION: In this survey of physician practice, the RS result was used to guide adjuvant treatment decision making in N+/ER+ breast cancer more often in patients with tumors less than 5 cm in size and one to three positive lymph nodes than in patients with larger tumors and four or more positive nodes and yielded an overall reduction in recommendations for chemotherapy
— id: 134927, year: 2011, vol: 7, page: 94, stat: Journal Article,

Cost-Effectiveness of 21-gene assay in node-positive, early-stage breast cancer
Vanderlaan, Burton F; Broder, Michael S; Chang, Eunice Y; Oratz, Ruth; Bentley, Tanya G K
2011 ;17(7):455-464, American journal of managed care
Objective: To assess impact on health outcomes and healthcare expenditures of adopting a 21-gene assay for women with early-stage, minimally node-positive, estrogen receptor-positive (N (1-3)/ER) HER2-negative breast cancer. Study Design: We adapted a deterministic decision-analytic model to estimate costs and quality-of-life outcomes associated with chemotherapy, adverse events, supportive care, recurrence, and second primary cancers for usual care compared with care determined by the 21-gene assay recurrence score, where 71% and 54% of women, respectively, were treated with adjuvant chemotherapy. Model input data were based on national statistics, published literature, physician surveys, and Medicare Part B prices. Methods: Annual numbers of events were multiplied by quality-adjusted life-years (QALYs) lost and costs to estimate net health and economic impacts of each strategy. Analyses were from a managed care payer perspective for the US population. Results: Patients receiving the assay were predicted to gain 0.127 QALY and save $4359 annually from avoiding chemotherapy, adverse events, supportive care, and secondary primary tumors. For a 2-million member plan, net gains were 4.44 QALYs/year and savings were $13,476/year. Cost savings were greater for the Medicare population. Although overall results were sensitive only to reduced impact of testing and chemotherapy costs, they were still highly cost-effective (incremental cost-effectiveness ratio <$20,000/QALY).Conclusions: Use of a 21-gene assay in patients with early-stage N (1-3)/ER HER2-negative breast cancer may improve health outcomes and add no incremental cost, thereby providing valuable insight for health plans, the Centers for Medicare and Medicaid Services, and clinicians regarding coverage policies and treatment decisions
— id: 136489, year: 2011, vol: 17, page: 455, stat: Journal Article,

Living with metastatic breast cancer: A global patient survey
Mayer M.; Hunis A.; Oratz R.; Glennon C.; Spicer P.; Caplan E.; Fallowfield L.
2010 ;7(9):406-412, Community Oncology
Worldwide, one-third of patients who present with early-stage breast cancer will go on to develop metastatic disease. Despite a serious diagnosis with a grave prognosis, treatment advances have meant that women are living longer with metastatic breast cancer. Although the clinical aspects of metastatic breast cancer have been well studied, little is known about the personal, psychosocial, and emotional experiences of women living with the disease. Because early-stage breast cancer is highly visible in the media and is a focus for most patient advocacy groups, women with metastatic disease feel isolated and alone. This paper presents the results of an international survey that questioned 1,342 women with metastatic breast cancer from 13 countries. The survey was designed to understand the nonmedical attitudes of patients living with metastatic breast cancer, identify perceived gaps in resources available to these patients, and define barriers to clinical trial enrollment and participation. 2010 Elsevier Inc. All rights reserved
— id: 115286, year: 2010, vol: 7, page: 406, stat: Journal Article,

Cardiac Safety Results of a Phase II Trial of Adjuvant Docetaxel/Cyclophosphamide Plus Trastuzumab (Her TC) in HER2+Early Stage Breast Cancer Patients
Jones, SE; Collea, RP; Oratz, R; Paul, D; Sedlacek, SM; Holmes, FA; Portillo, RM; Crockett, MW; Wang, Y; Asmar, L; O'Shaughnessy, JA; Robert, NJ
2009 DEC 15 ;69(24):792S-792S, Cancer research
— id: 106457, year: 2009, vol: 69, page: 792S, stat: Journal Article,

Evaluating the needs of women living with metastatic breast cancer: A global survey
Mayer, M; Hunis, A; Oratz, R; Glennon, C; Spicer, P; Caplan, E; Fallowfield, L
2009 MAR ;18(1):S70-S70, Breast
— id: 99257, year: 2009, vol: 18, page: S70, stat: Journal Article,

Importance of Providing Tailored Resources to Patients with Metastatic Breast Cancer: Results of the Global BRIDGE Survey
Mayer, M; Hunis, A; Oratz, R; Glennon, C; Spicer, P; Caplan, E; Fallowfield, L
2009 DEC 15 ;69(24):674S-674S, Cancer research
— id: 106454, year: 2009, vol: 69, page: 674S, stat: Journal Article,

Effect of 21-Gene Recurrence Score Results on Treatment Recommendations in Patients with Lymph Node-Positive, Estrogen Receptor-Positive Breast Cancer
Oratz, R; Chao, C; Skrzypczak, S; Kim, B; Broder, M
2009 DEC 15 ;69(24):602S-602S, Cancer research
— id: 106453, year: 2009, vol: 69, page: 602S, stat: Journal Article,

Feasibility and cardiac safety of pegylated liposomal doxorubicin plus trastuzumab in heavily pretreated patients with recurrent HER2-overexpressing metastatic breast cancer
Andreopoulou, Eleni; Gaiotti, Darci; Kim, Eugene; Volm, Matthew; Oratz, Ruth; Freedberg, Robin; Downey, Andrea; Vogel, Charles L; Chia, Stephen; Muggia, Franco
2007 Aug;7(9):690-696, Clinical breast cancer
BACKGROUND: Few studies have evaluated concomitant pegylated liposomal doxorubicin (PLD) plus trastuzumab as therapy for HER2-overexpressing metastatic breast cancer (MBC). This open-label, prospective, phase II trial assessed the safety and efficacy of this regimen, with cardiac tolerance as the principal focus. PATIENTS AND METHODS: Women with HER2-overexpressing recurrent MBC, baseline left ventricular ejection fraction >or= 55%, and no history of serious cardiac illness were eligible; preexisting cardiac risk factors, including previous anthracyclines and previous trastuzumab for MBC, were allowed. Patients received weekly trastuzumab and every-3-week PLD until progression, prohibitive toxicity, or patient refusal. Left ventricular ejection fraction was assessed during and after therapy. Grade 3/4 congestive heart failure (CHF) was monitored for premature closure. RESULTS: The trial closed after 2.5 years for slow accrual. Twelve patients were enrolled: 7 had received adjuvant anthracyclines; 9 had received previous MBC treatment, of whom 7 had received trastuzumab in combination with chemotherapy. Patients received a mean of 4.8 cycles of PLD; 8 patients experienced stable disease; 4 patients experienced progression. Mean left ventricular ejection fraction levels did not change substantially: 60.4%, 57%, 60.3%, and 56.8% at baseline, after cycle 2, after cycle 4, and after completion of treatment, respectively. No patients experienced grade 4 CHF. One patient discontinued treatment after grade 3 CHF. Three patients experienced grade 2 left ventricular dysfunction, of whom 2 discontinued treatment. Cardiac function improved in all 4 patients after going off study. Other adverse events were generally mild (grade 1/2) and infrequent. CONCLUSION: Pegylated liposomal doxorubicin plus trastuzumab might be an option for heavily pretreated patients with recurrent HER2-overexpressing MBC
— id: 75388, year: 2007, vol: 7, page: 690, stat: Journal Article,

Impact of a commercial reference laboratory test recurrence score on decision making in early-stage breast cancer
Oratz, Ruth; Paul, Dev; Cohn, Allen L; Sedlacek, Scot M
2007 Jul;3(4):182-186, Journal of Oncology Practice
PURPOSE: To investigate whether recurrence score (RS) as determined using a commercial reference laboratory test influences clinicians' treatment recommendations and eventual treatment in patients with early-stage breast cancer. METHODS: A retrospective analysis was performed on 74 patients from a community-based oncology practice with estrogen receptor (ER) -positive, lymph node (LN) -negative stage I or II breast cancer for which RS was obtained. Demographic and pathology information was extracted from medical records. Ten-year relapse-free survival was calculated using Adjuvant! Online. Treatment recommendations before the RS knowledge were compared with treatment recommendations after RS knowledge and to the treatment eventually administered. RESULTS AND CONCLUSION: A weak correlation was found between RS and both patient age and tumor size, modest correlation between RS and tumor grade, and modest correlation between RS and 10-year recurrence as determined by Adjuvant! Online. For 21% and 25% of patients, knowledge of the RS changed the clinicians' treatment recommendations and eventual treatment, respectively. The decision to change from hormone therapy to chemotherapy (with or without hormone therapy) was generally associated with high RS (high distant recurrence risk as determined by the commercial reference laboratory test), whereas the decision to change from chemotherapy to hormone therapy was generally associated with low RS (low distant recurrence risk as determined by the commercial reference laboratory test). Knowledge of the RS changed treatment recommendations and eventual treatment in patients with ER-positive/LN-negative early-stage breast cancer. Use of genomic-based prognosis may result in more accurate estimates of true recurrence risk than currently possible with commonly used prognostic factors (such as patient age, tumor size, and tumor grade) alone and thus lead to an increase in appropriate adjuvant therapy decision making
— id: 112565, year: 2007, vol: 3, page: 182, stat: Journal Article,

BRCA1 and BRCA2 mutations: 185delAG, 5382insC and 6174deIT; Ashkenazi founder or Jewish determinant?
Bersson, Y; Pearlman, A; Shajahan, S; Ostrer, H; Oratz, R
2006 FEB ;100(2):S180-S181, Breast cancer research & treatment
— id: 71009, year: 2006, vol: 100, page: S180, stat: Journal Article,

Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy
Demaria S; Volm MD; Shapiro RL; Yee HT; Oratz R; Formenti SC; Muggia F; Symmans WF
2001 Oct;7(10):3025-3030, Clinical cancer research
PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel therapy and if they correlate with response to treatment. Experimental Design: Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients. RESULTS: Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the tumor cell apoptotic response to the first dose of paclitaxel. CONCLUSIONS: These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment
— id: 24141, year: 2001, vol: 7, page: 3025, stat: Journal Article,

Increase in the lymphocytic infiltrate in breast cancer after neoadjuvant paclitaxel chemotherapy
Demaria, Sandra; Volm, M. D.; Shapiro, R. L.; Yee, H. T.; Oratz, R.; Formenti, S.; Muggia, F.; Symmans, W. F.
2000 ;43(41):334-334, Proceedings (American Association for Cancer Research)
— id: 109238, year: 2000, vol: 43, page: 334, stat: Journal Article,

Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: implications for early prediction of breast cancer response to neoadjuvant treatment
Symmans WF; Volm MD; Shapiro RL; Perkins AB; Kim AY; Demaria S; Yee HT; McMullen H; Oratz R; Klein P; Formenti SC; Muggia F
2000 Dec;6(12):4610-4617, Clinical cancer research
The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer
— id: 22642, year: 2000, vol: 6, page: 4610, stat: Journal Article,

Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine
Reynolds SR; Oratz R; Shapiro RL; Hao P; Yun Z; Fotino M; Vukmanovic S; Bystryn JC
1997 Sep 17;72(6):972-976, International journal of cancer
A critical requirement for cancer vaccines is that they stimulate CD8+ T cell responses. In this study, we tested the ability of a polyvalent melanoma vaccine to induce CD8+ T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1. Fifteen HLA-A2+ patients with resected malignant melanoma were immunized with the vaccine s.c. every 2-3 weeks. CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and Melan A/MART-1/(AAGIGILTV) were quantitated using a filter spot assay at baseline and following 4 immunizations. Vaccine immunization induced CD8+ T cells reacting to one or both of these peptides in 9 of the 15 (60%) patients. These cells were CD8+ and HLA-A2 restricted, as reactivity was abrogated by monoclonal antibodies (MAbs) to CD8 and class I HLA, but not by anti-CD4. All responding patients remained recurrence-free for at least 12 months (median 15 months, range 12 to >21 months), whereas melanoma recurred within 3-5 months in non-responders. The differences in outcome were unrelated to differences in disease severity or overall immunological competence between responders and non-responders. Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimulate CD8+ T cell responses in humans, and suggest that these responses are protective and surrogate markers of vaccine efficacy
— id: 12259, year: 1997, vol: 72, page: 972, stat: Journal Article,

IMPROVED SURVIVAL OF MELANOMA PATIENTS WITH DELAYED-TYPE HYPERSENSITIVITY RESPONSE TO MELANOMA VACCINE IMMUNIZATION
BYSTRYN, JC; ORATZ, R; ROSES, DF; HARRIS, MN; HENN, M; LEW, R
1991 APR ;96(4):549-549, Journal of investigative dermatology
— id: 51638, year: 1991, vol: 96, page: 549, stat: Journal Article,