1. Healthcare

Table of Contents
Volume 15, Number 1 February 2015
Illustration by Erin Moore
Original Studies
1
Inflammatory Breast Cancer Management in the National Comprehensive Cancer Network:
The Disease, Recurrence Pattern, and Outcome
Jennifer M. Matro, Tianyu Li, Massimo Cristofanilli, Melissa E. Hughes, Rebecca A. Ottesen, Jane C. Weeks,
Yu-Ning Wong
IBC is a unique entity with aggressive clinical features, predictable recurrence patterns, and poor prognosis.
The high rate of recurrence, especially in the CNS, suggests that new strategies for surveillance and follow-up
are needed for earlier detection or prevention of brain metastases.
8
Ixabepilone Alone or With Cetuximab as First-Line Treatment for Advanced/Metastatic
Triple-Negative Breast Cancer
Olivier Trédan, Mario Campone, Jacek Jassem, Rostislav Vyzula, Bruno Coudert, Carmen Pacilio, Jana Prausova,
Anne-Claire Hardy-Bessard, Ana Arance, Pralay Mukhopadhyay, Alessandra Aloe, Henri Roché
Efficacy of ixabepilone (n ¼ 40), or ixabepilone with cetuximab (n ¼ 39), as first-line treatment for
advanced/metastatic triple-negative breast cancer (TNBC) was assessed. Objective response rates of 30% and
35.9% were observed in the monotherapy and combination arms, respectively. Median progression-free survival
was 4.1 months in both arms. Monotherapy and combination therapy demonstrated similar levels of activity,
with predictable safety profiles.
16
Human Epidermal Growth Factor Receptor 2ePositive Breast Cancer: Heat Shock Protein 90
Overexpression, Ki67 Proliferative Index, and Topoisomerase II-a Co-amplification as
Predictors of Pathologic Complete Response to Neoadjuvant Chemotherapy With Trastuzumab
and Docetaxel
Emilio Bria, Jenny Furlanetto, Luisa Carbognin, Matteo Brunelli, Chiara Caliolo, Rolando Nortilli,
Francesco Massari, Serena Pedron, Erminia Manfrin, Francesca Pellini, Franco Bonetti, Isabella Sperduti,
Giovanni Paolo Pollini, Aldo Scarpa, Giampaolo Tortora
The correlation between Hsp90, Ki67, and TOPO2A and pCR was investigated in a series of 24 patients
with HER2-positive breast cancer. Neoadjuvant trastuzumab-docetaxel significantly decreased Ki67, and pCR
was significantly higher in patients with high Hsp90. These data suggest that Hsp90 may help to discriminate
patients with HER2-positive breast cancer as potential candidates to achieve pCR when receiving anti-Her2
agents.
24
Long-Term Follow-Up After Preoperative Trastuzumab and Chemotherapy for
HER2-Overexpressing Breast Cancer
Erica L. Mayer, Adrienne B. Gropper, Lyndsay Harris, Julie M. Gold, Leroy Parker, Irene Kuter, Steven Come,
Julie S. Najita, Hao Guo, Eric P. Winer, Harold J. Burstein
Documentation of long-term outcomes following HER2-directed therapy is an emerging research area.
We conducted a retrospective analysis of survival and toxicity outcomes using data from early trials of
neoadjuvant trastuzumab with chemotherapy. We find that the association between pathologic complete
response (pCR) and recurrence-free survival (RFS) persists at long-term follow-up, and that rare late cardiotoxicity
might occur in patients re-treated with cardiotoxic agents.
31
High Pathologic Complete Response in Her2-Positive, Early-Stage Breast Cancer to a Novel
Nonanthracycline Neoadjuvant Chemotherapy
Amelia B. Zelnak, Petros Nikolinakos, Jayanthi Srinivasiah, William Jonas, Andrew Pippas, Yuan Liu, Xiaoxian Li,
Mylin Torres, Ruth M. O’Regan, on behalf of the Georgia Center for Oncology Research and Education
The incorporation of HER2-directed therapies into neoadjuvant treatment for early-stage, HER2-positive
breast cancer has significantly improved the pathologic response rate. The combination of neoadjuvant
nab-paclitaxel followed by vinorelbine in combination with trastuzumab was evaluated in this single-arm clinical
trial. Among the 27 patients accrued, the pathologic complete response rate was 48.1%, demonstrating
promising clinical activity.
37
Clinical Characteristics and Outcome of Bone-Only Metastasis in Inflammatory and
Noninflammatory Breast Cancers
Megumi Kai, Takahiro Kogawa, Diane D. Liu, Tamer M. Fouad, Kazuharu Kai, Naoki Niikura, Limin Hsu,
Jie S. Willey, Richard L. Theriault, Vicente Valero, Naoto T. Ueno
The clinical course of bone metastasis in inflammatory breast cancer (IBC) has not been well studied. This
retrospective study analyzed 50 IBC and 147 non-IBC patients who had stage III disease on diagnosis of
primary breast cancer and then developed bone-only metastasis at first recurrence. We found that the IBC group
had a worse prognosis than did the non-IBC group.
43
Practice Patterns in the Delivery of Radiation Therapy After Mastectomy Among the
University of California Athena Breast Health Network
Jyoti Mayadev, John Einck, Sarah Elson, Hope Rugo, Shelley Hwang, Richard Bold, Parima Daroui,
Susan McCloskey, Catheryn Yashar, Danny Kim, Barbara Fowble
Practice patterns vary with the planning and delivery of radiation therapy after mastectomy (PMRT). We use a survey
to investigate the role of bolus and a boost. Fifty-five percent of the respondents routinely use a boost to the chest
wall in PMRT. Our study will help guide clinicians in the delivery of PMRT.
48
Everolimus-Induced Hematologic Changes in Patients With Metastatic Breast Cancer
Amy Chen, Li Chen, Abeer Al-Qaisi, Edward Romond, Mukta Awasthi, Vera Kadamyan-Melkumyan,
Suleiman Massarweh
We report on hematologic toxicities encountered during a clinical trial using everolimus for metastatic breast
cancer. Anemia, thrombocytopenia, and leukopenia were common but mild. Microcytosis and reduced red cell
hemoglobin content were consistently observed during treatment. Although total white blood cell counts
remained stable, there was a progressive decrease of lymphocyte percentage over time with a trend for
increased neutrophils.
54
Second Cancer, Breast Cancer, and Cardiac Mortality in Stage T1aN0 Breast Cancer Patients
With or Without External Beam Radiation Therapy: A National Registry Study
Jason C. Ye, Weisi Yan, Paul Christos, Dattatreyudu Nori, Kun-San C. Chao, Akkamma Ravi
The Surveillance, Epidemiology, and End Results (SEER) database was reviewed for long-term toxicities of radiation
therapy (RT) in women with T1aN0 breast cancer (BC). No increase in cardiac or secondary cancer mortalities
was found in patients who had RT, suggesting the rarity of these events. Women with early-stage BC eligible
for breast conservation therapy should not be dissuaded based on the fear of late radiation toxicity.
60
Oral Ridaforolimus Plus Trastuzumab for Patients With HER2þ Trastuzumab-Refractory
Metastatic Breast Cancer
Milton Seiler, Isabelle Ray-Coquard, Bohuslav Melichar, Denise A. Yardley, Rui X. Wang, Pierre F. Dodion,
Mark A. Lee
Resistance to trastuzumab treatment is potentially mediated by aberrant phosphatidylinositide 3-kinase
(PI3K)/AKT signaling; ridaforolimus may overcome trastuzumab resistance by inhibiting PI3K signaling. A
single-arm phase IIb trial was conducted to evaluate the efficacy and safety of ridaforolimus-trastuzumab in such
resistance in patients with human epidermal growth factor receptor 2epositive (HER2þ) trastuzumab-refractory
metastatic breast cancer (MBC). The combination showed antitumor activity and may allow for combination with
cytotoxic agents that could increase efficacy.
66
Breast Cancer Leptomeningeal Metastasis: The Results of Combined Treatment and the
Comparison of Methotrexate and Liposomal Cytarabine As IntraeCerebrospinal Fluid
Chemotherapy
Anna Niwinska, Halina Rudnicka, Magdalena Murawska
The aim of this study was to assess the outcome of 149 patients with breast cancer and leptomeningeal
metastasis (LM) and to compare the efficacy of intrathecal methotrexate and liposomal cytarabine. Among
treatment methods, only systemic therapy prolonged survival in these patients. Survival of patients treated
intrathecally with methotrexate and those treated with liposomal cytarabine was comparable.
73
Comparison of Toxicity Experienced by Older Versus Younger Patients Enrolled in Breast
Cancer Clinical Trials
Caroline Mariano, Mia Francl, Janice Pope, Linda Wong, Howard J. Lim, Caroline Lohrisch
The present study examined whether elderly patients who enroll in breast cancer clinical trials experience
more toxicity than do younger patients. A total of 46 trials, including 799 patients, open at the British Columbia
Cancer Agency (BCCA), Vancouver Center, were reviewed. Overall, the elderly patients did
not experience increased toxicity; however, they were underrepresented in trials containing cytotoxic
chemotherapy. Appropriate selection of elderly patients using eligibility criteria, self-selection, and/or clinician
assessment will allow safe participation of elderly patients in breast cancer trials.
80
BRCAness Predicts Resistance to Taxane-Containing Regimens in Triple Negative Breast
Cancer During Neoadjuvant Chemotherapy
Sadako Akashi-Tanaka, Chie Watanabe, Tomoko Takamaru, Takashi Kuwayama, Murasaki Ikeda,
Hiroto Ohyama, Miki Mori, Reiko Yoshida, Rikako Hashimoto, Sawada Terumasa, Katsutoshi Enokido,
Yuko Hirota, Hiromi Okuyama, Seigo Nakamura
We investigated BRCAness in the biopsy and surgical specimens from 73 patients with breast cancer,
taken before and after taxane-containing neoadjuvant chemotherapy. All tumors that progressed on taxanecontaining regimens had a poor prognosis; all had BRCAness and most were triple negative. Identifying
BRCAness can help predict the response to taxane-containing regimens.
Available Exclusively Online at
www.clinical-breast-cancer.com
e1
Improved Clinical Outcomes Associated With Vitamin D Supplementation During Adjuvant
Chemotherapy in Patients With HER2þ Nonmetastatic Breast Cancer
Simon B. Zeichner, Tulay Koru-Sengul, Nikesh Shah, Qingyun Liu, Nathan J. Markward, Alberto J. Montero,
Stefan Glück, Orlando Silva, Eugene R. Ahn
Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including
the disruption of human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK
pathway. We performed a retrospective review of patients who received VD supplementation during
neoadjuvant chemotherapy (n ¼ 134) and those who did not (n ¼ 112). In our final multivariate model, VD use
was associated with improved disease-free survival (DFS) (hazard ratio [HR], 0.36; 95% confidence interval
[CI], 0.15-0.88); P ¼ .026). To the best of our knowledge, our study is the first to report a significant
improvement in DFS for patients who received VD supplementation concurrently with trastuzumab-based
chemotherapy for HER2-positive (HER2þ) nonmetastatic breast cancer.
e13
Association Between Ligands and Receptors Related to the Progression of Early Breast
Cancer in Tumor Epithelial and Stromal Cells
Vivian Labovsky, Leandro Marcelo Martinez, Kevin Mauro Davies, Hernán García-Rivello,
María de Luján Calcagno, Ayelén Matas, Valeria Beatriz Fernández Vallone, Alejandra Wernicke,
Hosoon Choi, Norma Alejandra Chasseing
We have demonstrated the association between RANKL, IL-6, SDF-1, and CCL-2 in tumor epithelial cells and
their receptors in spindle-shaped stromal cells, as well as between TRAIL, RANKL, and CCL-2 in spindle-shaped
stromal cells and their receptors in tumor epithelial cells from 63 patients with breast cancer (I/II stage). These
molecules may be implicated in breast cancer progression during the early stage of the disease.
e23
Significance of Fine Needle Aspiration Cytology and Vacuum-Assisted Core Needle Biopsy
for Small Breast Lesions
Satoko Nakano, Masahiko Otsuka, Akemi Mibu, Toshinori Oinuma
Of 455 ultrasonography-guided vacuum-assisted core needle biopsy (VAB) cases of small breast lesions,
fine-needle aspiration cytology (FNAC) was performed before VAB in 248 cases [54.5%] yielding
inconclusive results in 133 cases [53.6%]. Excisional biopsy was performed in 17 benign VAB cases, because
of FNAC overdiagnosis in 6 cases [35%]. Pathological, not cytological, examination should be
the initial diagnostic approach.
e27
Chemotherapy Use and Surgical Treatment by Receptor Subtype in Node-Negative T1a and
T1b Female Breast Cancers, Iowa SEER Registry, 2010- to 2012
Mary C. Schroeder, Charles F. Lynch, Taher Abu-Hejleh, Elizabeth A. Chrischilles, Alexandra Thomas
Small node-negative breast tumors represent a growing portion of breast cancer diagnoses. As treatment
recommendations have evolved for this group, we report the first SEER data on chemotherapy and surgical
choice by breast cancer receptor subtype for these tumors. In Iowa from 2010 to 2012, chemotherapy use
correlated with recurrence risk for the 1687 women included. Relatively high rates of mastectomy were seen.
e35
Variability in Measuring the Ki-67 Labeling Index in Patients With Breast Cancer
Shinya Yamamoto, Takashi Chishima, Yuka Mastubara, Shouko Adachi, Fumi Harada, Youko Toda,
Hitoshi Arioka, Naoki Hasegawa, Yukio Kakuta, Kentaro Sakamaki
The aim of the present study was to evaluate the Ki-67 labeling index variability using different measurement
methods and specimens. The results differed according to the method and specimen types used, and the
indication for chemotherapy also changed accordingly.
e41
Cysteine Rhenium Colloid: A Novel Radiocolloid for Identifying Sentinel Lymph Nodes in
Breast Cancer Surgery
Biniam Kidane, Pamela L. Zabel, Vaibhav Gupta, Caroline Whiston, Frances Wright, Muriel Brackstone
Cysteine rhenium colloid (CRC) requires less medical isotope than standard sulfur colloid (SC) for sentinel
lymph node biopsy (SNB). Our retrospective cohort study on 1205 consecutive early, clinically node-negative
breast cancer patients who underwent SNB with either isotope suggests CRC is an alternative to SC in
detecting sentinel lymph nodes, and uses less medical isotope.
e47
The Oncologic Safety and Practicality of Breast Conservation Surgery in Large Breast Tumors
5 Centimeters or More
Conor M. Sugrue, Peadar S. Waters, Karl J. Sweeney, Carmel Malone, Kevin Barry, Michael J. Kerin
The surgical management of large breast cancers is controversial. Improvements in neoadjuvant chemotherapy
along with utilisation of oncoplastic surgical techniques have enabled breast conservation in women with
larger breast cancers. This study demonstrates oncologic equivalence of BCS and mastectomy for tumors
5 cms. The re-excision was higher in this cohort in comparison to smaller tumors in other studies. Extensive
DCIS was a risk factor for inadequate margins.
e55
Effects of Second and Subsequent Lines of Chemotherapy for Metastatic Breast Cancer
In Hae Park, Keun Seok Lee, Jungsil Ro
Continuing cytotoxic chemotherapy is justified in metastatic breast cancer. However, the clinical effects of
successive treatment have not been evaluated. In the present study, we assessed 240 patients with metastatic
breast cancer who received multiple lines of cytotoxic chemotherapy regimens. We confirmed that the
beneficial effects of subsequent chemotherapy for patients with a durable response from previous treatment.
e63
Invasive Lobular Carcinoma Arising in a Hamartoma of the Breast: A Case Report
Julie Lambert, Naim Jerjir, Jan Casselman, Luc Steyaert
e67
Breast Cancer in Male-to-Female Transgender Patients: A Case for Caution
Maryam Sattari
e71
Breast Cancer in a RAD51D Mutation Carrier: Case Report and Review of the Literature
Jennifer L. Baker, Richard B. Schwab, Anne M. Wallace, Lisa Madlensky
e77
Papulopustular Acneiform Eruptions Resulting From Trastuzumab, a HER2 Inhibitor
Johanna Sheu, Elena B. Hawryluk, Georgia Litsas, Manisha Thakuria, Nicole R. LeBoeuf