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Elizabeth A Mittendorf,
Thomas A Buchholz,
Susan L Tucker,
Funda Meric-Bernstam,
Henry M Kuerer,
Ana M Gonzalez-Angulo,
Isabelle Bedrosian,
Gildy V Babiera, Karen Hoffman,
Min Yi,
Merrick I Ross,
Gabriel N Hortobagyi,
Kelly K Hunt
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ABSTRACT: : This study was performed to evaluate long-term local-regional control rates after breast-conserving therapy (BCT) for patients undergoing surgery before or after neoadjuvant chemotherapy.
: There were 2983 patients who underwent segmental mastectomy with whole-breast irradiation from 1987 to 2005. Clinicopathological and outcome data were reviewed, and comparisons were made between those undergoing surgery before and those undergoing surgery after neoadjuvant chemotherapy.
: There were 2331 patients (78%) who underwent surgery first and 652 (22%) received neoadjuvant chemotherapy. Patients receiving neoadjuvant chemotherapy had more advanced disease at baseline and more adverse clinicopathological features. The 5- and 10-year local-regional recurrence (LRR)-free survival rates were 97% [95% confidence interval (CI), 96-98) and 94% (95% CI, 93-95) for surgery first and 93% (95% CI, 91-95) and 90% (95% CI, 87-93) after neoadjuvant chemotherapy (P < 0.001). However, there were no differences in LRR-free survival rates when comparing the presenting clinical stage (P = NS). Of 607 patients presenting with clinical stage II/III disease, chemotherapy downstaged 313 patients (52%) to pathological stage 0/I disease; 294 (48%) had residual stage II/III disease. In multivariate analysis, an age less than 50 years, clinical stage III, grade 3, estrogen receptor (ER)-negative disease, estrogen receptor-positive disease without receipt of endocrine therapy, lymphovascular invasion, multifocal disease on pathology, and close/positive margins were associated with LRR. Use of neoadjuvant chemotherapy was not significant when added to the model. Adjusting for adverse factors, there were no differences in LRR between patients who underwent surgery before and those who underwent neoadjuvant chemotherapy after surgery.
: LRR after BCT is driven by tumor biology and disease stage. Appropriately selected patients can achieve high rates of local-regional control with BCT with either upfront surgery or surgery after neoadjuvant chemotherapy.
Annals of surgery 02/2013; 257(2):173-9. · 7.90 Impact Factor
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Abigail S Caudle,
Kelly K Hunt,
Susan L Tucker, Karen Hoffman,
Sarah M Gainer,
Anthony Lucci,
Henry M Kuerer,
Funda Meric-Bernstam,
Ruchita Shah,
Gildy V Babiera,
Aysegul A Sahin,
Elizabeth A Mittendorf
[show abstract]
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ABSTRACT: The ACOSOG Z0011 trial has been described as practice-changing. The goal of this study was to determine the impact of the trial on surgeon practice patterns at our institution.
This is a review of practice patterns comparing the year before release of Z0011 to the year after an institutional multidisciplinary meeting discussing the results. Patients meeting Z0011 inclusion criteria were identified. Clinicopathologic data were compared between the cohorts.
There were 658 patients with clinical T1-2 tumors planned for breast conservation: 335 in the pre-Z0011 cohort and 323 post-Z0011. Sixty-two (19 %) patients were sentinel lymph node (SLN) positive in the pre-Z0011 group versus 42 (13 %) post-Z0011 (p = 0.06). Before Z0011, 85 % (53/62) of SLN-positive patients underwent axillary node dissection (ALND) versus 24 % (10/42) after Z0011 (p < 0.001). After Z0011, surgeons were more likely to perform ALND on patients with larger tumors (2.2 vs. 1.5 cm, p = 0.09), lobular histology (p = 0.01), fewer SLNs (1 vs. 3, p = 0.09), larger SLN metastasis size (4 vs. 2.5 mm, p = 0.19), extranodal extension present (20 vs. 6 %, p = 0.16), or a higher probability of positive non-SLNs (p = 0.03). Surgeons were less likely to perform intraoperative nodal assessment post-Z0011 (26 vs. 69 %, p < 0.001) resulting in decreased median operative times for SLN-negative patients (79 vs. 92 min, p < 0.001).
Surgeons at our institution have implemented Z0011 results for the majority of patients; however, clinicopathologic factors still impact the decision to perform ALND. Z0011 results have significantly impacted practice by decreasing rates of ALND, use of intraoperative nodal evaluation, and operative times.
Annals of Surgical Oncology 07/2012; 19(10):3144-51. · 4.17 Impact Factor
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Abigail S Caudle,
Tse-Kuan Yu,
Susan L Tucker,
Isabelle Bedrosian,
Jennifer K Litton,
Ana M Gonzalez-Angulo, Karen Hoffman,
Funda Meric-Bernstam,
Kelly K Hunt,
Thomas A Buchholz,
Elizabeth A Mittendorf
[show abstract]
[hide abstract]
ABSTRACT: Breast cancers of different molecular subtypes have different survival rates. The goal of this study was to identify patients at high risk for local-regional recurrence according to response to neoadjuvant chemotherapy and surrogate markers of molecular subtypes in patients undergoing breast conserving therapy (BCT).
Clinicopathologic data from 595 breast cancer patients who received neoadjuvant chemotherapy and BCT from 1997 to 2005 were identified. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression determined by immunohistochemistry were used to construct the following subtypes: ER+ or PR+ and HER2- (hormone receptor (HR)+/HER2-; 52%), ER+ or PR+ and HER2+ (HR+/HER2+; 9%), ER- and PR- and HER2+ (HR-/HER2+; 7%) and ER- and PR- and HER2- (HR-/HER2-; 32%). Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used for multivariate analysis (MVA).
After a median follow-up of 64 months, the five-year local-regional recurrence (LRR)-free survival rate for all patients was 93.8%. The five-year LRR-free survival rates varied by subtype: HR+/HER2- 97.0%, HR+/HER2+ 95.9%, HR-/HER2+ 86.5% and HR-/HER2- 89.5% (P = 0.001). In addition to subtype, clinical stage III disease (90% vs. 95% for I/II, P = 0.05), high nuclear grade (92% vs. 97% with low/intermediate grade, P = 0.03), presence of lymphovascular invasion (LVI) (89% vs. 95% in those without LVI, P = 0.02) and four or more positive lymph nodes on pathologic examination (87% vs. 95% with zero to three positive lymph nodes, P = 0.03) were associated with lower five-year LRR-free survival on univariate analysis. On MVA, HR-/HER2+ and HR-/HER2- subtypes and disease in four or more lymph nodes were associated with decreased LRR-free survival. A pathologic complete response (pCR) was associated with improved LRR-free survival.
Patients with HR+/HER2- and HR+/HER2+ subtypes had excellent LRR-free survival regardless of tumor response to neoadjuvant chemotherapy. Patients with HR-/HER2+ and HR-/HER2- subtypes with poor response to neoadjuvant chemotherapy had worse LRR-free survival after BCT. Additional study is needed to determine the impact of trastuzumab on local-regional control in HER2+ tumors. Our data suggest that patients with HR-/HER2- subtype tumors not achieving pCR may benefit from novel strategies to improve local-regional control.
Breast cancer research: BCR 05/2012; 14(3):R83. · 5.24 Impact Factor
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Abigail S Caudle,
Kelly K Hunt,
Henry M Kuerer,
Funda Meric-Bernstam,
Anthony Lucci,
Isabelle Bedrosian,
Gildy V Babiera,
Rosa F Hwang,
Merrick I Ross,
Barry W Feig, Karen Hoffman,
Jennifer K Litton,
Aysegul A Sahin,
Wei Yang,
Gabriel N Hortobagyi,
Thomas A Buchholz,
Elizabeth A Mittendorf
Annals of Surgical Oncology 02/2011; 18(9):2407-12. · 4.17 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Single-institution data suggest that treatment with radiation and axillary lymph node dissection (ALND) may be an appropriate alternative to mastectomy for T0N+ breast cancer. Population-based multi-institutional data supporting this approach are lacking.
The cause-specific survival (CSS) and overall survival (OS) of women with T0N+M0 ductal, lobular, or mixed breast cancer in the Surveillance, Epidemiology, and End Results database from 1983 to 2006 were analyzed. Groups were defined as: 1) no ALND, mastectomy, or RT (observation); 2) ALND only; 3) mastectomy plus ALND with or without postmastectomy radiation (Mast); and 4) breast-conserving therapy (BCT) with ALND and radiation (BCT).
In total, 750 of 770,030 patients with breast cancer had T0N+M0 disease (incidence, 0.10%), and 596 of those patients underwent ALND (79.5%). Patients who underwent Mast or BCT (n = 470) had a 10-year OS rate of 64.9% compared with 58.5% for patients who underwent ALND only (n = 126; P = .02) and 47.5% for patients who underwent observation only (n = 94; P = .04). The 10-year CSS rate was 75.7% for patients who underwent BCT versus 73.9% for patients who underwent Mast (P = .55). In multivariate analysis of CSS for patients who underwent Mast or BCT, the following factors were correlated with an unfavorable outcome: positive estrogen receptor status (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.24-0.96; P = .04), >/=10 positive lymph nodes (HR, 5.7; 95%CI, 2.4-13.4; P </= .01), and <10 resected lymph nodes (HR, 42.9; 95%CI, 1.2-7.1; P = .02). Mast did not improve CSS compared with BCT (HR, 1.09; 95%CI, 0.57-2.1; P = .79).
Definitive locoregional treatment with either Mast or BCT improved the outcome of patients with T0N+breast cancer, and no difference in survival was observed between the treatments. Cancer 2010. (c) 2010 American Cancer Society.
Cancer 09/2010; 116(17):4000-6. · 4.77 Impact Factor
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ABSTRACT: The insulin-like growth factor I (IGF-I) signaling pathway has been shown to play an important role in several aspects of cancer biology, including metastasis. The aim of this study was to define the contribution of serum (endocrine) and local (tumour microenvironment) IGF-I on osteosarcoma tumour growth and metastasis, a cancer that is known to be dependent on the IGF-I axis. To test this hypothesis, we evaluated the primary tumour growth and metastatic progression of K7M2 murine osteosarcoma cells injected to a genetically engineered mouse [liver-specific IGF-I deficient (LID)] in which serum IGF-I levels are reduced by 75%, while maintaining expression of IGF-I in normal tissues. We first demonstrated that IGF-I in the tumour and the tumour-microenvironment were maintained in the LID mice. Within this designed model, there was no difference in primary tumour growth or in pulmonary metastasis in LID mice compared to control mice. Furthermore, there was no difference in the number or localization of single metastatic cells immediately after their arrival in the lungs of LID mice and control mice, as analysed by single cell video microscopy. Collectively, these data suggest that marked reduction in serum IGF-I is not sufficient to slow the progression of either primary or metastatic models of osteosarcoma.
International Journal of Cancer 12/2008; 124(9):2042-9. · 5.44 Impact Factor
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Patrick Mansky,
Andrew Arai,
Pamela Stratton,
Donna Bernstein,
Lauren Long,
James Reynolds,
Donna Chen,
Seth M Steinberg,
Neil Lavende, Karen Hoffman,
Paul C Nathan,
Rebecca Parks,
Elizabeth Augustine,
Usha Chaudhry,
Joanne Derdak,
Lori Wiener,
Lynn Gerber,
Crystal Mackall
[show abstract]
[hide abstract]
ABSTRACT: To assess health and musculoskeletal function in survivors of pediatric sarcomas.
Thirty-two individuals treated for Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), or non-rhabdomyosarcoma soft tissue sarcomas (NR-STS) with multi-modality therapy were enrolled on this cross-sectional study. Median age at the time of therapy was 15.4 years (range 7.1-34.2), median age at the time of analysis was 37.4 years (17.5-55.4), and median duration of time elapsed from completion of therapy was 17.3 years (2.9-32.6). Participants underwent assessments of musculoskeletal functioning, cardiac function, metabolic and lipid analyses, renal and gonadal function, and psychological evaluation.
This cohort of sarcoma survivors shows expected locoregional limitations in function of the area affected by sarcoma, and impaired global musculoskeletal functioning as evidenced by limited endurance and limited overall activity levels. The cohort also demonstrated substantial rates of cardiac dysfunction, elevated body fat index, hyperlipidemia, chronic psychological distress, and infertility in men (76%) and premature menopause (49%) in women.
Sarcoma survivors demonstrate diminished locoregional and global musculoskeletal functioning which likely limit occupational opportunities and socioeconomic health. In addition, the combination of diminished cardiac reserve, limited activity levels, and lipid dysregulation in sarcoma survivors suggests that this population is at increased risk for cardiovascular disease, even many years following completion of sarcoma therapy. Sarcoma survivors may benefit from life long follow-up for cardiovascular disease and from occupational counseling upon completion of therapy.
Pediatric Blood & Cancer 03/2007; 48(2):192-9. · 1.89 Impact Factor
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ABSTRACT: To describe the inter-relationships among impairments, performance, and disabilities in survivors of pediatric sarcoma and to identify measurements that profile survivors at risk for functional loss.
Prospective, cross-sectional.
Research facility.
Thirty-two participants in National Cancer Institute clinical trials.
Not applicable.
Range of motion (ROM), strength, limb volume, grip strength, walk velocity, Assessment of Motor and Process Skills (AMPS); Human Activity Profile (HAP), Sickness Impact Profile (SIP), standard form of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36); and vocational attitudes and leisure satisfaction.
Twenty of 30 survivors tested had moderate or severe loss of ROM; 13 of 31 tested had 90% or less of predicted walk velocity; all of whom had trunk or lower-extremity lesions. Women with decreased ROM (r=.50, P=.06) or strength (r=.74, P=.002) had slow gait velocity. Sixteen of 31 tested were more than 1 standard deviation below normal grip strength. Eighteen had increased limb volume. These 18 had low physical competence (SF-36) (r=-.70, P=.001) and high SIP scores (r=.73, P=.005). AMPS scores were lower than those of the matched normed sample (P<.001). HAP identified 15 of 30 who had moderately or severely reduced activity. Leisure satisfaction was higher in the subjects (P<.001). Eight reported cancer had negatively impacted work and 17 reported that it negatively impacted vocational plans.
Survivors with lower-extremity or truncal lesions and women with decreased ROM and strength likely have slow walk velocity, low exercise tolerance, and high risk for functional loss. They should be identified using ROM, strength, limb volume, and walk time measures.
Archives of Physical Medicine and Rehabilitation 12/2006; 87(12):1611-7. · 2.28 Impact Factor
