24.07 TAK228 Enhances Antitumor Activity of Eribulin in Triple Negative Breast Cancer

Posted on January 31, 2019

N. Owusu-Brackett1, K. W. Evans1, A. Akcakanat1, E. Yuca1, E. Ileana Dumbrava1, F. Janku1, F. Meric-Bernstam1  1University Of Texas MD Anderson Cancer Center,Houston, TX, USA

Introduction: Phosphatase and tensin homologue (PTEN) negatively regulates the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Triple negative breast cancers (TNBC) are often PTEN-deficient, making mTOR a compelling target. We evaluated the efficacy of catalytic mTOR inhibitor TAK228 alone and in combination with eribulin in triple negative breast cancers (TNBC) with and without PTEN loss.

Methods: We tested TAK228 in combination with eribulin in a panel of TNBC cell lines with cell proliferation assays. Western blot analysis was performed to assess PTEN status and PI3K pathway inhibition. In vivo, antitumor efficacy of TAK228 as a single agent as well as in combination with eribulin was evaluated.

Results: Five of eight triple negative breast cell lines were sensitive to TAK228, independent of PIK3CA/PTEN status. Western blotting demonstrated inhibition of mTORC1/2 signaling as demonstrated by decreased phosho-AKT, phospho-S6 and phospho-4EBP1. In vitro, TAK228 was synergistic with eribulin in all eight TNBC cell lines. The combination of TAK228 and eribulin did not enhance apoptosis but increased G2/M growth arrest (p<0.001). In vivo, TAK228 led to modest growth inhibition in TNBC derived xenografts with no tumor regression observed. In two TNBC PDXs with PTEN loss, one with intrinsic eribulin sensitivity, another eribulin resistance, TAK228 in combination with eribulin did not enhance in vivo efficacy. In a third PTEN-negative TNBC model, eribulin alone achieved disease stabilization, but the combination of TAK228 and eribulin led to significantly smaller tumor volumes compared to eribulin alone (p<0.001).

Conclusion: TAK228 enhances the antitumor efficacy of eribulin in TNBC models in vitro, and enhanced in vivo activity in selected models. Further study is needed to determine the potential of this combination, and optimal patient selection strategies.

 

24.06 An innovative approach to protecting immune function in breast cancer through Hsp90 inhibition

Posted on January 31, 2019

T. Wang1, C. Subramanian1, M. Cohen1  1University Of Michigan,General Surgery,Ann Arbor, MI, USA

Introduction: Breast cancer is the second leading cause of cancer-related death in women in the US. To date, use of immunotherapy has been difficult due to decreased mutational burden in breast cancer compared to other cancers such as melanoma. Hsp90 has been an exciting target for the development of anti-tumor agents, as multiple cancer signaling pathways can be disrupted simultaneously through Hsp90 inhibition; however, current Hsp90 inhibitors have significant immunosuppressive effects by decreasing dendritic cell maturation, antigen uptake, and tumor recognition by T cells. Recently our group has developed novel Hsp90 inhibitors that target only the carboxy-teminus (KU758) or are selective to the beta-isoform of Hsp90 (KUNB31). We hypothesize that these novel approaches to Hsp90 inhibition will have decreased immunosuppressive effects (due to their improved selectivity for client proteins) compared to traditional N-terminal inhibitors (17-AAG) and would be more ideal drugs for combination with immunotherapy.

Methods: Validated MCF7 (ER+) and MDA-MB-231 (triple neg) breast cancer cells were treated with 17-AAG, KU758, and KUNB31 for 30 hr. Dendritic cells (DC) were isolated from murine bone marrow and plated on a 96-well plate. The supernatant from the treated cells was then transferred to DCs for 24 hours. IL-6, TNA-α, and TGF-β secretion was measured by ELISA assay. SPSS software was used for statistical analysis and all experiments were repeated in triplicate.

Results: IL-6 secretion from DCs was decreased by exposure to 17-AAG treated MCF7 cells compared to untreated cells by 45.9% (p=0.05). Similar results were observed in exposure to 17-AAG treated MDA-MB-231 cells (52.6% decrease, p=0.001). In contrast, IL-6 levels were not significantly changed with exposure of DCs to both cell types treated with KU758 or KUNB31, except slightly at high concentrations >10uM of KUNB31 (decreased by 15.2%, p=0.13). In DCs exposed to Hsp90 inhibitor-treated MCF7 cells, there was decreased TNF-α expression with all drugs, but the greatest effect was noted with 17-AAG (decreased by 39.6%, p=0.07). TNF-α expression was significantly decreased by 81.9% (p=0.01) from DCs exposed to 17-AAG treated MDA-MB-231 cells. In contrast, no significant decrease in either TNF-α expression or TGF-β secretion was seen with KU758 and KUNB31 treatment. See Figure 1.

Conclusion: Compared to N-terminal inhibitors, our novel approach to Hsp90 inhibition may be better targets for combination with immunotherapy agents due to their lack of immunosuppressive effects. Additional studies in translational models are warranted to further validate this significant opportunity and support future clinical applications.

24.04 The First HSP90β Inhibitor Differentially Regulate Wild & Mutant p53 Expressing Breast Cancer Cells

Posted on January 31, 2019

C. Subramanian1, N. Zhang1, B. B. Blagg2, M. S. Cohen1  1University of Michigan,General Surgery,Ann Arbor, MI, USA 2University of Notre Dame,Department Of Chemistry And Biochemistry,Notre Dame, INDIANA, USA

Introduction: Heat shock protein 90 (Hsp90) is a molecular chaperone that is critical for several cellular processes including the folding, maturation and degradation of client proteins involved in the development of cancers (including the breast cancer) and their metastatic spread. Current Hsp90 inhibitors in clinical trials non-selectively target all four isoforms of Hsp90 and have shown detrimental toxicities. Through an innovative structure guided design, our collaborative group has recently developed the first Hsp90β isoform specific inhibitors. During the initial screens with our lead β  specific Hsp90 inhibitor, KUNB105, we noted that cancer cells with wild type (wt) p53 were more sensitive to the drug than p53 mutant (mt) cells. Therefore, we have hypothesized that it is the differential effect in p53 pathway proteins to Hsp90β  selective inhibition that leads to this selective effect on p53 wt breast cancer (BC) cells compared to mt p53 cell lines.  

Methods: Validated BC cell lines MCF7 (p53 wt) and MDA-MB-231 (p53 mt) were treated with KUNB105 and viability of cells were measured using cell TiterGlo. Changes in expression levels of Hsp90 clients were analyzed by western. Apoptosis was measured using RealTime-Glo Annexin V Apoptosis and Necrosis Assay. Changes in cancer pathway genes was analyzed after treatment of cells with KUNB105 using Qiagen Cancer Pathway Profiler assay. Prism software was used for statistical analysis and all experiments were repeated in triplicate.

Results: Viability of MDA-MB-231 and MCF7 cells after treatment with KUNB105 showed an IC50 value of 20.5 & 8.2 μ M respectively. Analysis of p53-pathway by Western showed dose dependent increase in p53 (3-5 fold) and mdm2 (2-3 fold) starting from 10  μ M KUNB105 treatment for MCF7 cells whereas the levels of p53 did not show observable change even at the highest concentration of 30 μ M KUNB105 (p<0.001) for MDA-MB-231. By contrast, the cell cycle dependent protein p21 showed dose dependent upregulation starting at 1μ M KUNB105 (2- fold, p<0.01) in both cell lines indicating that KUNB105 treatment leads to cell cycle arrest. Evaluation of the effect of KUNB105 treatment on apoptosis showed increase in luminescence starting from 2 h (30000-33000 compared to around 12000 for the control, p<0.001) and peaked at 10 h (50,000-54,000, p<0.001) for both the cells indicating significant induction of apoptosis. Evaluation of cancer pathway after KUNB105 treatment of BC cells showed differential expression of genes in cell cycle (AURKA, CCND2, E2F4, MK167, WEE1, STM1), DNA damage and repair (ERCC5 and GADD45G) as well as apoptosis (BCL2L11).

Conclusions: Our results indicate that KUNB105 has selectivity to p53 wt BC and induces apoptosis through p53 pathway-specific mechanistic differences between wt and mt BC cell lines. Further studies related to this unique targeting effect are needed for translational applications of this promising and novel Hsp90β  inhibitor.

24.03 Orthotopic implantation develop better triple negative breast cancer Patient-Derived Xenograft

Posted on January 31, 2019

M. Okano1, M. Oshi1, K. Takabe1  1Roswell Park Cancer Institute,Surgical Oncology,Buffalo, NY, USA

Introduction: Patient-Derived Xenograft (PDX) has come into the limelight of breast cancer research to be used for pre-clinical studies. Some of its weaknesses are its poor engraftment rates and slow growths, which often limits its use as an avatar of the donor patient. Therefore, improvement of the models especially in engraftment and tumor growth are in urgent need. We hypothesized that orthotopically implanted tumors (Ortho) engraft better, grow faster and larger compared from subcutaneously implanted PDX (SQ), which is the standard model. 

Methods: NSG mice were used to generate PDX. 2 tumors were derived from brain metastasis (B-met), and the others were from primary breast cancers. 3 tumors were ER(+)HER2(-) and 7 tumors were triple negative (TN). Both of B-met tumors are ER(+)HER2(-). Tumor “engraftment” was defined as tumorigenesis of palpable tumor after implantation regardless of time it took.

Results:The overall engraftment rate was significantly better in Ortho than SQ (77.8% (n=137/176) vs. 50.7% (n=79/156), p<0.01). Ortho tumors grew remarkably larger than SQ tumors. The mean tumor weight was significantly heavier in Ortho than SQ (0.75g vs 0.14g, p<0.01). Ortho tumors demonstrated more abundant mitotic figures compared with SQ tumors (19.2 vs 7.9, p<0.01). Ortho tumors had more Ki-67 positive cells than SQ tumors (31.5 vs 21.8, p=0.015). The tumor weight was significantly larger when implantation was made to the 2nd or to the 4th mammary fat pad (0.73g vs 0.96g, p=0.02). Tumor engraftment of 1st generation was low (24.8% (n=32/129)), but the rate of 2nd (82.2% (n=46/56)) and 3rd (80.6% (n=58/72)) generation was significantly increased (p<0.001). The time it took for the 1st generation to grow was the longest between 3 generations (1st; 152days, 2nd; 66days, 3rd; 63days, p<0.01). The mean tumor weight was significantly higher in Ortho sites among all generations (1st -3rd) of TN cancer (0.2g, 1.1g vs 0.8g, respectively, p<0.01). ER positive cancer xenograft revealed significantly lower engraftment rate (26.7% (n=12/45) vs 65.1% (n=216/332), p<0.01), slower tumor growth, and lighter tumor weight (0.18g vs 0.47g, p<0.001) than TN xenograft. The xenograft from brain-metastasized breast cancer also showed higher engraftment rate in MP than SQ (94.4% (n=68/72) vs. 69.4% (n=50/72), p<0.01) although was not the organ that brain metastasis originally grew. The brain metastasis tumors also demonstrated higher tumor weight in MP than SQ (0.28g vs 0.54g, p<0.001). The brain metastasis tumors grew faster than primary tumor (52days vs 95days, p<0.01). 

Conclusion:Orthotopical implantation showed better take rate, greater tumor size and weight than heterotopic implantation, regardless of the cancer subtypes and their sources.

 

15.19 Methotrexate Use In Patients With Granulomatous Mastitis

Posted on January 31, 2019

B. Caballero2, J. Sugandi1,2, R. K. Viscusi1,2  1Banner- University of Arizona,Department Of Surgery,Tucson, AZ, USA 2University Of Arizona,College Of Medicine,Tucson, AZ, USA

Introduction:  Granulomatous mastitis (GM) is a rare, benign, chronic inflammatory disease of the breast that usually affects women of child bearing age. The most common clinical symptoms are a palpable breast mass associated with overlying erythema, induration, pain or drainage. Imaging is non-specific and histopathology is needed for confirmative diagnosis. The etiology is unclear, but an autoimmune reaction is favored and it has been linked to prior contraceptive use, a history of pregnancy and breastfeeding. Given the limited knowledge of etiology, initial treatment of this benign, yet locally aggressive disease remains controversial. Observation alone, antibiotics, surgical excision, steroids alone, and immunosuppressive agents have all been described in the literature. There is no consensus on treatment but knowing GM is generally a self-limited disease and surgery can be associated with poor cosmetic outcomes, a non-invasive alternative such as methotrexate (MTX) is a viable option. 

Methods:  A retrospective chart review of patients with histologically confirmed GM between January 2013 and December 2017 was analyzed to identify response to MTX treatment. Eight adult female patients, age range 29-57, were diagnosed with GM via excisional or core breast biopsy. Methotrexate treatment was planned for all 8 patients with confirmed GM. Liver function tests and a full blood count were evaluated during treatment course. Treatment protocol included MTX administered at 2.5-10 mg orally together with folic acid in one dose, once a week. 

 

Results: On physical exam, a palpable breast mass was detected on 8 patients. All patients underwent ultrasound examination and after diagnosis of GM was confirmed, MTX + folic acid treatment was initiated. Treatment was administered for 3-15 months. One patient discontinued MTX due to plans to conceive. None of the patients developed complications from MTX and no recurrence was observed during follow up periods. Patients noted relief of symptoms including, erythema, breast tenderness and nipple discharge following 30-60 days of MTX treatment. 

Conclusion: Evidence in most literature has shown most patients with GM have a troublesome course of recurrence. There is no consensus on treatment but non-invasive alternatives such as steroids and methotrexate are good options. More cases using methotrexate alone or in combination with corticosteroids are needed to confirm those results. Ultimately, treatment depends on the size of the lesions and symptom severity. Prompt diagnosis and treatment with methotrexate can often treat the disease or provide symptomatic improvement without subjecting patients to multiple trials of medications that could pose risks of adverse effects. 
 

05.20 Characteristics of Breast Cancer in Young Patients Based on a Saudi Tertiary Hospital Experience

Posted on January 31, 2019

A. Alhefdhi1, S. AlNefaie1, O. Almalik1  1King Faisal Specialist Hospital and Research Center (KFSH), and AlFaisal University,Breast And Endocrine Surgery/General Surgery,Riyadh, RIYADH, Saudi Arabia

Introduction: Breast cancer accounts for 26% of the cancers in Saudi Arabia, with a median age of 49 years at diagnosis. However, no published literature about treating breast cancer in a young Saudi population.The aim of this study is to explore the characteristic features of breast cancer in Saudi patients 40 years of age or younger.

Methods: A five-year retrospective review conducted, including all patients diagnosed with breast cancer and operated at a single tertiary hospital.

Results:A total of 1026 were identified. Among them, 230 cases (22%) meet our inclusion criteria with a mean age of 34±5 years. The majority had IDC (85.7%), followed by DCIS in (6.5%), malignant phylloids in (3.1%),  ILC in (1.7%), metaplastic carcinoma in (1.3%), intracystic papillary carcinoma in (0.9%), (0.4%) of borderline phylloid, and  (0.4%) of Angiosarcoma. Only (14%) found to have a positive family history of breast cancer, and (15%) found to have metastatic disease at diagnosis. The recurrence rate was (17.4%). Moreover, the majority underwent lumpectomy with/without SLND/ALND (38%), followed by SSM (22%), simple mastectomy with/without SLNB (13%), MRM (10%), palliative surgery (6.5%), nipple sparing mastectomy (4.5%), wire localization lumpectomy (4%),  then bilateral surgery (3%). Among the patients with IDC (51.3%) had grade 3 cancer, (70%) had a positive ER, (53%) had a positive PR,  (26%) had positive Her-2,  (24%) had triple negative.

Conclusion:Our data suggested that 1/4th of breast cancer cases are 40 years or younger. Further studies are needed to confirm our findings and to exclude possible genetic mutations.

 

05.19 Metaplastic Breast Cancer: A Rare and Challenging Diagnosis

Posted on January 31, 2019

S. M. Nazarian1, M. M. Goldbach1, M. K. Pomponio1, C. Huang1, A. D. Williams2, J. Tchou1  1University of Pennsylvania,Surgery,Philadelphia, PA, USA 2Lankenau Medical Center,Surgery,Wynnewood, PA, USA

 

Introduction:
Metaplastic carcinoma is a heterogeneous group of breast malignancies characterized by a mixture of different pathologic subtypes.  Due to their rarity, the clinical behavior of these aggressive tumors is not well characterized. 

Methods:
A single institution database was queried for all cases of non-metastatic metaplastic breast cancer diagnosed between January 1, 2009 and December 31, 2015.  Those with no nodes examined were excluded.  Stata/MP 14.2 (College Station, TX) was used for all analyses.

Results:

Metaplastic breast cancer was identified in 42 patients during the study period, all of whom were women.  Median age was 57.5 years, interquartile range (IQR) 46, 68.  Median clinical stage at presentation was 2 (IQR 1.5, 2). 14.6% of patient were estrogen receptor positive; 12.2% were progesterone receptor positive but only 2.8% expressed human epidermal growth factor receptor 2.  Lymphovascular invasion was present in 12.9% of patients.  

 

In terms of treatment, 13.9% received neoadjuvant therapy.  61.9% went on to receive mastectomies; 23.5% underwent axillary lymph node dissection.  

 

At last contact (median 382 days ago (IQR 229, 763)), 30 of 42 (71.3%) patients were alive.  Ten (24.4%) of patients experienced recurrence, including 1 local, 2 regional and 7 distant recurrences.

Conclusion:
Metaplastic breast cancer remains a rare and challenging tumor.  This single-institution case series provides an opportunity for further characterization.  

05.18 Impact of Margins on Re-excision Rates for Breast-Conserving Surgery

Posted on January 31, 2019

V. Danthuluri2, S. Martin4, E. B. Malone3, J. S. Richman3, R. Lancaster1, C. C. Parker1  4University Of Alabama at Birmingham,Birmingham, Alabama, USA 1University Of Alabama at Birmingham,Surgical Oncology,Birmingham, Alabama, USA 2University Of Alabama at Birmingham,School Of Medicine,Birmingham, Alabama, USA 3University Of Alabama at Birmingham,Gastrointestinal Surgery,Birmingham, Alabama, USA

Introduction:  The surgical options available for patients diagnosed with breast cancer are mastectomy vs breast conserving surgery (BCS), also known as lumpectomy. The goal of BCS is to remove the breast cancer while minimizing loss of normal breast tissue. Prior to 2014, there was no general consensus on what constituted an acceptable negative margin width for BCS, though a common practice was to require ≥ 2mm clear margins for invasive cancer and ductal carcinoma in situ (DCIS). The lack of clear guidelines resulted in patients returning for a re-excision surgery, which increased the risk of complications, emotional stress, and healthcare costs. In 2014, a consensus statement based on a concurrent meta-analysis for margins for patients undergoing BCS with whole breast irradiation in Stage I and II invasive breast cancer was published by the American Society for Radiation Oncology (ASTRO) and the Society of Surgical Oncology (SSO) stating that as long as all margins are clear of invasive cancer, or “no ink on tumor”, the risk of ipsilateral breast tumor recurrence is minimized, and obtaining wider margin widths does not significantly lower this risk. The standard accepted margin for DCIS remains ≥ 2mm. The aim of this retrospective review was to examine the re-excision rate in breast cancer patients undergoing BCS at a single academic institution in the year 2015 to analyze the impact of standard “no ink on tumor” guidelines in reducing re-excisions.

Methods:  All women, ≥ 18 years old, with invasive breast cancer who underwent a lumpectomy in 2015 at a single institution were included if the margin for DCIS (if present) was ≥ 2mm. Descriptive statistics were used to examine the cohort’s sociodemographics and tumor characteristics. Patients who could have avoided a re-excision based on the new guidelines were identified based on invasive surgical margins that were < 2mm. Once identified, counts and medians were used to describe the categorical and continuous variables, respectively.

Results: Out of 188 invasive breast cancer patients in the cohort, mean age was 61.5yo, 67% were Caucasian, and 63% of the patients had their index surgery performed at this institution. There were 40 (21%) patients who underwent a re-excision. A total of 3 patients (1.6%) could have been affected by the guidelines of “no ink on tumor”, ultimately these 3 patients underwent additional surgery. Out of these patients, 2 converted to mastectomy based on patient preference, and the remaining patient underwent re-excision based on surgeon preference.

Conclusion: The 2014 guidelines were relevant only for the treatment of a small proportion of patients. The majority of breast cancer patients undergoing BCS at our institution had margins ≥ 2mm for invasive cancer; therefore, the new consensus of “no ink on tumor” for invasive cancer did not impact our re-excision rate in 2015.

 

05.17 Breast-Conserving Surgery for Lobular Carcinoma In Situ Variants: A Single Institution’s Experience

Posted on January 31, 2019

D. I. Hoffman1, P. J. Zhang2, J. Tchou1,3  1Perelman School of Medicine at the University of Pennsylvania,Department Of Surgery,Philadelphia, PA, USA 2Perelman School of Medicine at the University of Pennsylvania,Department Of Pathology,Philadelphia, PA, USA 3Perelman School of Medicine at the University of Pennsylvania,Abramson Cancer Center, Rena Rowan Breast Center,Philadelphia, PA, USA

Introduction: Lobular carcinoma in situ (LCIS) found on core needle biopsy is a benign lesion that confers increased lifetime risk of breast cancer but generally does not require further surgery. In contrast, non-classic LCIS (NC-LCIS), which includes high-grade variants with pleomorphism or necrosis, warrants surgical excision. In patients pursuing breast-conserving surgery (BCS) for NC-LCIS, the need for wide surgical margins to prevent recurrence is controversial. We therefore characterized the surgical management and outcomes of women diagnosed with NC-LCIS at a large, academic medical center.

Methods:  A retrospective database query was conducted to identify female patients seen at our institution from 2008–2018 with a biopsy diagnosis of NC-LCIS. Patients were excluded if NC-LCIS was diagnosed in the background of invasive breast carcinoma or ductal carcinoma in situ (DCIS). Clinicopathologic, surgical, and follow-up data were collected by chart review. Rates of upstage, re-excision, and recurrence were calculated.

Results: We identified 26 patients with NC-LCIS diagnosed on biopsy. The cohort was mostly white, the median age was 54 years (range 40–70), and half were postmenopausal. None were known carriers of breast cancer gene (BRCA) mutations, but 10 patients had a first-degree family history of breast cancer. Almost all (24/26) presented with an abnormal screening mammogram, 22 of which had suspicious calcifications. 80.8% (21/26) of patients initially pursued breast conservation, while 19.2% (5/26) underwent immediate mastectomy. At definitive surgery, 11.5% (3/26) were upstaged to DCIS or invasive carcinoma. Among 19 patients with a final diagnosis of NC-LCIS undergoing BCS, 47.4% (9/19) had at least one re-excision and five patients converted to completion mastectomy. In patients receiving BCS without completion mastectomy, 64.3% (9/14) had final surgical margins that were negative for NC-LCIS, while 35.7% (5/14) had close (<1mm) or positive margins. No recurrences in patients with negative margins at definitive surgery were observed. One patient with positive margins developed a local recurrence 8.3 years after surgery, and one patient with close margins did 2.2 years after surgery. All patients with a final diagnosis of NC-LCIS were alive at time of analysis with no evidence of progression to invasive carcinoma, mean follow-up time 4.5 years (range 20 days–10.5 years).

Conclusion: We presented the clinical outcomes of one of the largest single institution series of NC-LCIS, a rare diagnosis. In patients with a final diagnosis of NC-LCIS pursuing breast conservation, re-excisions are common and negative margins can be challenging. However, when negative margins are achieved, recurrence risk is low.

05.16 Frequency of PI3K pathway activation, CCNE1 amplification, Rb1 and ESR1 mutations in breast cancer

Posted on January 31, 2019

T. Takeshita1, E. Katsuta1, L. Yan2, K. Takabe1  2Roswell Park Cancer Institute,Biostatistics & Bioinformatics,Buffalo, NY, USA 1Roswell Park Cancer Institute,Breast Surgery, Surgical Oncology,Buffalo, NY, USA

Introduction:  Endocrine therapies are one of the essential treatments for estrogen receptor (ER)-positive breast cancer, particularly in combination with targeted therapies. It is now established that endocrine therapy with targeted therapies, such as, CDK4/6 inhibitors and mTOR inhibitors, is a mainstay of treatments for ER-positive metastatic breast cancer (MBC). ESR1 mutation is a resistance factor of endocrine therapy and it is a useful biomarker predicting an effect of the treatment, but it is not certain whether or not it has same utility when used with targeted therapies. RB1 mutation and amplification of cyclin E1 (CCNE1) are now known as resistance factors of CDK4/6 inhibitors. PI3K pathway is known to play an important role in ER positive breast cancer and its activity affects both endocrine therapy and molecular target therapy. Therefore, it is noteworthy whether coexistence of ESR1 mutation and these genetic abnormalities is a predictor of effect of these combination therapies. Here we studied the frequency of PI3K pathway alterations (PIK3CA mutation/amplification and PTEN loss), Rb1 mutation, and amplification of CCNE1 with ESR1 mutation in ER-positive breast cancer.

Methods: We analyzed gene abnormalities using an ER-positive primary breast cancer (PBC) cohort from TCGA data (n = 525) and a MBC cohort (n = 216).

Results: In the PBC cohort, PI3K pathway alterations were recognized at 40%, Rb1 mutation at 0.9%, amplification of CCNE1 at 10%, and ESR1 mutation at 0.9%. As expected, presence of ESR1 mutation was very low and it was difficult to verify the relationship with other factors. In the MBC cohort, the frequency of PI3K pathway alterations, Rb1 mutation, and amplification of CCNE1 was almost unchanged, but ESR1 mutation was found to be 20%. Some cases with genomic alterations coexisting with ESR1 mutation were found, suggesting the possibility of showing resistance to combination therapies.

Conclusion: We showed the clinically important frequency of genomic alterations coexisting with ESR1 mutation in ER positive breast cancer cohort.

05.15 The Influence of Age on the Biology and Prognosis of Breast Atypia

Posted on January 31, 2019

A. R. Sergesketter1, S. M. Thomas2,3, A. M. Gupta1, O. M. Fayanju1,2, L. H. Rosenberger1,2, C. S. Menendez1,2, R. A. Greenup1,2, T. Hyslop2,3, E. S. Hwang1,2, J. K. Plichta1,2  1Duke University Medical Center,Department Of Surgery,Durham, NC, USA 2Duke Cancer Institute,Durham, NC, USA 3Duke University Medical Center,Department Of Biostatistics,Durham, NC, USA

Introduction:  Several prognostic variables and risk factors for invasive breast cancer have been shown to be age-related. However, the association between age and risk of cancer for women with high-risk breast lesions, such as atypia, is controversial. The aim of this study was to compare the prevalence of breast atypia and risk of upgrade or progression to breast cancer by age.

Methods:  Adult women diagnosed with breast atypia [lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH)] at a major academic institution from 2008-2017 were identified. Patients were stratified by age at initial atypia diagnosis: <50 years, 50-70 years, and >70 years. Differences between age groups were tested using Fisher’s Exact and Kruskal-Wallis tests. Logistic regression was used to estimate the association of age with risk of upgrade to or subsequent cancer diagnosis after adjustment.

Results: Among the 530 atypia patients (median age 54y) identified, 31.1% were <50y (N=165), 58.1% were 50-70y (N=308), and 10.8% were >70y (N=57). ADH was the most common finding in 75.1% of patients (N=398), followed by LCIS in 13.2% (N=70) and ALH in 11.7% (N=62). When comparing types of atypia by age, older women >70y were more likely to present with ADH, while women <70y were more likely to present with ALH or LCIS (overall p=0.04). Of the 471 women diagnosed with atypia by needle biopsy, 14.9% (N=70) were upgraded to breast cancer (invasive or in situ) at the time of surgical excision, which did not vary by age (p=0.33). Of the 70 women upgraded, 61.4% were to ductal carcinoma in situ (DCIS) and 37.1% to invasive disease, which was similar between age groups (p=0.4). The use of chemoprevention after an atypia diagnosis was also similar between all age groups (overall uptake 27.2%, p=0.55). During the follow-up of the remaining 458 women with atypia (median 49 months), 15.7% (N=72) developed a subsequent diagnosis of breast cancer (invasive and in situ) unrelated to the initial biopsy, which did not vary by age (p=0.66). Of those who subsequently developed breast cancer, 45.8% were diagnosed with DCIS and 54.2% with invasive disease, which was similar for all age groups (p=0.93). The unadjusted time to subsequent diagnosis of breast cancer did not vary by age (log rank p=0.41, Figure 1). After adjustment, age was not associated with upgrade to or subsequent diagnosis of breast cancer (both p>0.05).

Conclusion: Among women with breast atypia, age may influence the type of atypia diagnosed, but does not appear to be associated with risk of upgrade or subsequent progression to breast cancer.

 

05.14 Treatment Response to Neoadjuvant Therapy in Invasive Ductal Carcinoma and Invasive Lobular Carcinoma

Posted on January 31, 2019

L. Qu1, C. Perez1, C. Godellas1, F. Vaince1  1Loyola University Chicago Stritch School Of Medicine,Surgery,Maywood, IL, USA

Introduction:

Neoadjuvant treatment (NAT) for locally advanced breast cancer can downstage disease prior to surgery, thereby allowing patients to become candidates for breast conservation therapy. Tumor histology has been suspected to impact treatment response to NAT, though current data is limited. We compared response to NAT in patients with invasive ductal carcinoma (IDCA) and invasive lobular carcinoma (ILCA).

Methods:

An IRB-approved retrospective chart review was conducted on breast cancer patients treated with NAT followed by surgery at an academic tertiary care center between September 2013 and July 2018. Two cohorts (IDCA and ILCA) were identified and compared with specific attention to tumor biology, nodal status, and operation performed. Fisher’s Exact Test was used for statistical analyses.

Results:

A total of 231 patients were identified, of which 206 (89%) had IDCA and 25 (11%) had ILCA. Of IDCA patients who underwent NAT followed by surgery, 34% achieved pathologic complete response (pCR) compared to 12% of ILCA patients (p=0.02). There were no significant differences between the IDCA and ILCA cohorts in terms of axillary downstaging or rate of breast conservation surgery. Lobular tumors were larger at presentation (4.1 cm compared to 3.8 cm for ductal tumors) and showed smaller mean decrease in tumor size following NAT (35% compared to 62% for ductal tumors). Fifty percent of patients with IDCA had triple negative (TN) or human epidermal growth factor receptor 2 (Her2+) disease; of these, 48% achieved pCR. Conversely, only 12% of patients with ILCA had TN or Her2+ disease. The majority (88%) of ILCA patients were hormone receptor (HR)+/Her2-. Amongst the HR+/Her2- subgroup, there were no significant differences between the IDCA and ILCA cohorts in terms of pCR, axillary downstaging, or rate of breast conservation surgery. However, the mean decrease in tumor size following NAT was more comparable in this subgroup at 49% and 41% for IDCA and ILCA tumors, respectively.

Conclusion:

Patients with IDCA are more likely to achieve pCR to neoadjuvant therapy than patients with ILCA, though there are no significant differences between groups in terms of axillary downstaging to node-negative disease and rate of breast conservation surgery following NAT. A clinical and pathologic response to NAT can still be anticipated in ILCA tumors, particularly considering the influence of tumor biology. Consequently, a neoadjuvant approach to ILCA should not be dismissed on histology alone.

 

05.13 Factors Associated With Neoadjuvant Therapy Use in Invasive Lobular Carcinoma of the Breast

Posted on January 31, 2019

R. A. Mukhtar1, J. M. Wong1, K. E. Fahrner-Scott1, C. Ewing1, M. D. Alvarado1, L. J. Esserman1, J. C. Boughey3, A. J. Chien4  1University Of California – San Francisco,General Surgery,San Francisco, CA, USA 3Mayo Clinic,General Surgery,Rochester, MN, USA 4University Of California – San Francisco,Hematology/Oncology,San Francisco, CA, USA

Introduction:  Although neoadjuvant therapy (NAT) increases breast conserving surgery rates in women with breast cancer, its effectiveness in invasive lobular carcinoma (ILC) has been questioned. Since surgeons must identify which patients may benefit from a neoadjuvant approach, we sought to determine factors associated with NAT in women with ILC. Additionally, we explored associations with neoadjuvant chemotherapy versus neoadjuvant endocrine therapy use. 

Methods:  We queried a prospectively maintained surgical database and identified 679 cases of clinical stage 1-3 ILC treated at our institution from 1981-2017. We collected patient characteristics, tumor size, subtype, stage, therapy, and era of treatment.  Data were analyzed in Stata 14.2 using t-tests for continuous variables, and chi-squared test for categorical variables. 

Results: NAT was used in 21.8% of cases, with 12.4% receiving neoadjuvant chemotherapy and 9.4% receiving neoadjuvant endocrine therapy.  Overall, women receiving NAT were significantly younger (57.3 vs 60.4 years, p = 0.0065), had larger tumors (2.9 vs 2.2 cm, p=0.0058), and had tumor subtype other than ER+ PR+ Her2- (p<0.001). NAT use significantly increased over time, initially consisting exclusively of neoadjuvant chemotherapy, but with an increasingly higher proportion of neoadjuvant endocrine therapy use in recent years (p=0.007, Figure).

We then analyzed ER+ Her2- cases (n=546, with 438 PR+ and 108 PR -), since NAT is questioned most in this group. Among these patients, NAT was significantly more common in younger women (56.8 vs 60.4 years, p=0.0033), and those with PR- disease (37.1% vs 17.8%, p<0.001). There was no difference in tumor size, treatment era, tumor grade, or histologic subtype. Lastly, within the ER+ Her2- cases who received NAT, those who received neoadjuvant chemotherapy were significantly younger (52.1 vs 61.9 years, p<0.0001), more likely to be premenopausal (45.1% vs 21.2%, p=0.01), and less likely to be diagnosed within the last 10 years (p=0.002).  Among premenopausal women with ER+ Her2- ILC receiving NAT, the only factor associated with receipt of neoadjuvant endocrine therapy versus chemotherapy was era of diagnosis, with significantly less chemotherapy in the last ten years (p=0.034).

Conclusion: Although many studies question the utility of NAT in ILC, our data show a striking change in management patterns over time, with a steady increase in NAT use and a shift from neoadjuvant chemotherapy to neoadjuvant endocrine therapy, even in premenopausal women. The long term impact of this new management strategy in ILC, and the utility of the information garnered about response to therapy, warrant additional study. 
 

05.12 Placement of Subcutaneous Central Venous Ports in Breast Cancer Patients: Does Side Matter?

Posted on January 31, 2019

C. A. Isom1, P. Bream3, R. N. Ahmed2, K. C. Gallagher2, S. Walia2, R. Kauffmann4  1Vanderbilt University Medical Center,General Surgery,Nashville, TN, USA 2Vanderbilt University,School Of Medicine,Nashville, TN, USA 3Vanderbilt University Medical Center,Radiology,Nashville, TN, USA 4Vanderbilt University Medical Center,Surgical Oncology & Endocrine Surgery,Nashville, TN, USA

Introduction:

The placement of subcutaneous central venous ports in breast cancer patients has become a common practice. Historically, ports have been placed on the side contralateral to the breast cancer due to concern about increased risk of complications with ipsilateral port placement. There have been only a few small studies evaluating complication rates between ports placed ipsilateral vs. contralateral to the breast cancer. We sought to determine if there was a difference in port complications or lymphedema rates by port location.

Methods:

A single institution retrospective review was conducted of adult (>18yrs) female patients undergoing central venous port placement for breast cancer treatment between 2012 and 2016. Patients that had ports placed by both surgery and interventional radiology were included. Patients were excluded if they had ports placed at another facility, their initial breast pathology was unavailable or treatment history was unavailable prior to their port placement.

Results:

A total of 581 females were identified with a mean age of 52.9 ±11.7 years. Ipsilateral ports were placed in 41 patients (7.1%). Ipsilateral ports were more likely to be placed via the internal jugular vein (56.1%) while contralateral ports were more likely to be placed in the subclavian vein (67.2%), p=0.002. There was no difference between type of breast surgery (p=0.997), axillary surgery (p=0.087) or administration of adjuvant radiation therapy (p=0.684) for patients that had ipsilateral vs contralateral ports. There was no difference in breast cancer stage at diagnosis but it did tend towards significance (p=0.0587). Ipsilateral ports were more likely to be on the right side, 73.2% vs 51.1% (p=0.006). Contralateral port were more likely to be placed for neoadjuvant therapy while ipsilateral ports were more likely to be placed for adjuvant therapy. Port complications requiring intervention occurred in 3(7.3%) patients with ipsilateral ports and 33(6.1%) patients with contralateral ports (p=0.73). Upper extremity lymphedema occurred in 8(20%) patients with ipsilateral ports and in 118(21.9%) of patients with contralateral ports (p=0.639).

Conclusion:

There was no difference in port complication or lymphedema rates between patients who had ports placed on the ipsilateral side compared to contralateral side for breast cancer treatment.

 

05.11 Evaluating Breast Intraductal Papilloma and Risk of Upgrade at Surgical Excision.

Posted on January 31, 2019

S. Martin1, J. Richman2, C. Parker2, R. Lancaster2  1University of North Carolina at Charlotte,Charlotte, NC, USA 2University of Alabama at Birmingham,Department Of Surgery,Birmingham, AL, USA

Introduction: Breast intraductal papillomas (IP) are epithelial fibrovascular stalks occurring within the ducts of the breast. IPs may be symptomatic or asymptomatic and have a variable presentation with many detected by routine breast screening. Controversy exists regarding the need for surgical excision of these lesions with differing rates of upgrade reported (2.2-15.7%) at excision. IPs with atypia or pathologic discharge are typically surgically removed due to increased concern for upgrade. In this retrospective single institution study, we quantified the upgrade rates of IPs at surgical excision. Additionally, we sought to identify factors associated with increased risk of upgrade of IPs to precancerous or invasive malignancy at surgical.

Methods: We retrospectively reviewed data from women who had received a core needle biopsy diagnosis of intraductal papilloma between 2010 and 2016 at a single institution. Any women who had concurrent diagnosis of contralateral or ipsilateral breast cancer were excluded. Data regarding imaging characteristics and patient factors were collected.

Results: The study included 195 cases of intraductal papilloma diagnosed by biopsy (mean age 55.6, range 28-99);  22 biopsies (16.1%) had atypia and 19 (13.9%) had bloody nipple discharge. 137 of the women (70.3%) underwent surgical excision. Among the women who underwent surgical excision, 4 (2.9%) were upgraded to ductal carcinoma in situ. No upgrade to invasive cancer was identified.  Of the 58 women who did not undergo excision, 1 (1.7 %) developed a subsequent invasive malignancy. Overall, 4 women (2.1 %) developed DCIS or an invasive carcinoma within the years (1.5-4 years) post-IP diagnosis.

Conclusion: This study reveals a low upgrade rate for IPs suggesting that surgical excision may not be necessary in the majority of cases. Additional studies to include larger patient numbers focusing on specific risk factors associated with upgrade would be beneficial.

 

05.10 Does Oncotype DX Utilization Decrease Chemotherapy Use in Men with Early Stage Breast Cancer?

Posted on January 31, 2019

C. McGreevy1, A. D. Williams1, L. De La Cruz1, J. Tchou1  1University Of Pennsylvania,Division Of Endocrine And Oncologic Surgery,Philadelphia, PA, USA

Introduction:  Prior to the advent of the 21-gene recurrence score assay, Oncotype DXTM (oDX), adjuvant chemotherapy would likely be recommended in individuals who were diagnosed with node negative estrogen/progesterone receptor (HR) positive, Her-2/neu (Her2) negative breast cancer (BC) with less favorable prognostic features such as younger age of diagnosis ( < 50 years), larger tumor size (T > 1 cm), and higher histologic grade (intermediate or high grade). We hypothesize that the use of oDx in patients with these clinical factors is associated with decreased chemotherapy recommendation and utilization. Several studies have shown that oDx impacted chemotherapy recommendation in women. However, whether oDx use in men reduces chemotherapy recommendation is unclear. We sought to elucidate chemotherapy recommendation and utilization in men with node negative breast HR+ Her2- breast cancer with less favorable prognostic features in this study.

Methods:  Retrospective review using the National Cancer Database identified 34,178 patients diagnosed with node negative, HR +, Her2 negative breast cancer who were diagnosed at age < 50 with T > 1 cm, tumor grade intermediate or high between 2010-2015. Of the 34,174 patients, 33,958 were female breast cancer (FBC) and 216 were male breast cancer (MBC). Demographics, tumor characteristics, oDX, chemotherapy, and hormone therapy data were collected, and we compared the chemotherapy utilization in FBC and MBC stratified by oDX testing.

Results: A smaller proportion of MBC patients received oDX testing compared to FBC (39% vs 47% p=.02). FBC patients that received oDX testing tended to be older, treated at an academic center, have smaller tumor size, and intermediate grade. There were no differences in tumor characteristics of MBC patients who received oDX vs those that did not. The distribution of oDX scores was similar between MBC and FBC ( p=.97). Both MBC and FBC had decreased chemotherapy utilization and increased hormone therapy utilization with oDX testing (Table 1). 

Conclusion: As oDX is a gene expression assay which is likely agnostic to gender differences, applying oDX testing to MBC is reasonable. We have shown that the use of oDX in MBC is associated with decreased chemotherapy recommendation/utilization. Our results align with previous reports that oDX decreases chemotherapy utilization in women. Our data also showed that the oDX distribution is similar in FBC and MBC thus refuting the assumption that MBC has a more aggressive gene expression profile. Further investigation into the impact of oDX on clinical outcomes in MBC with prospective multi-center studies would be of great value.

 

05.09 Higher Rates of Mastectomy in Her2-Neu Positive Invasive Lobular Versus Ductal Carcinoma

Posted on January 31, 2019

E. C. Shenvi1, J. Murphy1, R. Sarkar1, S. Blair1  1University Of California – San Diego,San Diego, CA, USA

Introduction:  Invasive lobular carcinomas (ILC) represent a minority of HER2-positive breast cancers, and may respond differently to systemic treatment. We investigated if lobular histology was associated with breast conservation rates and response to neoadjuvant therapy.

Methods:  Using the National Cancer Database (NCDB) for years 2006-2015, we selected patients with invasive breast cancer and Her2 positivity. Rates of mastectomy and response to neoadjuvant therapy were examined as a function of histology by logistic regression controlling for demographics and tumor characteristics.  Statistical analysis was done in R.

Results:   There were 142,909 patients in the NCDB with invasive Her2-positive carcinomas, of which 126,702 had ductal and 4,887 had lobular histology.  ILC was associated with an OR of 1.34 for ultimately having a mastectomy instead of breast conservation (95% confidence interval[CI] 1.23-1.46 p<<0.001) among those treated surgically.  Pathologic response to neoadjuvant therapy was available for only 28,196 subjects.  Lobular histology had lower rates of complete response to neoadjuvant systemic therapy, with OR of 0.81 (95% CI 0.68 – 0.97, p=0.022)., any response to neoadjuvant therapy OR of 0.65 (95% CI 0.47 – 0.92,  p=0.012). Among patients given chemotherapy, lobular histology was again associated with increased rates of mastectomy, OR 1.34 (95% confidence interval 1.22-1.46, p<<0.001) controlling for clinical stage and patient demographics. Mortality data in this subset was available for 106,288 patients.  Lobular histology was associated with increased mortality, OR 1.24 (1.09-1.42,  p=0.001.  This effect persisted when controlling for surgical treatment, OR 1.23 (1.07-1.42, p=0.003).

Conclusion:  Her2-Neu positive ILC represents a small minority of breast cancers.  It appears to have an intermediate response to neoadjuvant therapy compared to Her2-neu positive IDC, which is known to have high pathologic complete response rates. Clinicians should use this data when counseling patients on treatment options and appropriate expectations for surgical treatment. 
 

05.08 Evolution of Indications for Nipple-sparing Mastectomy: Trends in Patient Selection Over A Decade

Posted on January 31, 2019

A. J. Bartholomew1, K. F. Griffith1, G. M. Lassiter1, S. Mehra1, M. Sosin2, D. L. Caragacianu1, S. C. Willey1, E. A. Tousimis1  2NYU Langone Health,Hansjörg Wyss Department Of Plastic Surgery,New York, NY, USA 1MedStar Georgetown University Hospital,Breast/Surgery,Washington, DC, USA

Introduction:  Rates of nipple-sparing mastectomy (NSM) continue to increase due to improved cosmesis and demonstrated oncologic safety. Successful outcomes have led to expanded patient selection in those who were traditionally considered to be non-ideal candidates. This study aims to characterize changes in patient selection for NSM over one decade at a single institution.

 

Methods: A single-institution, retrospective chart review identified all NSMs occurring from Jan 2008 through Dec 2017. Patient demographics traditionally included for patient selection criteria were collected including age, BMI, smoking history, breast size, ptosis, and history of radiation. Macromastia was defined as breast size larger than a C cup, obesity was defined as BMI > 30, smoking status was defined at the time of diagnosis, and ptosis was recorded as clinically significant if grade two or higher. Primary outcomes were differences in patient demographics evaluated by chi-squared and Student’s t-test across the decade in two bins (2008-2012 vs. 2013-2017). History of radiation was evaluated by breast, while all other variables were evaluated at the patient level.

 

Results: A total of 492 patients and 847 breasts were included in the final cohort spanning ten years. From 2008 to 2012, 157 (31.9%) patients underwent NSM, while 335 (68.1%) NSMs occurred from 2013 to 2017. The mean age of the cohort was 46.1 years (SD = 10.2), BMI was 23.6 kg/m2 (SC = 4.0), obesity was present in 39 (7.9%) of patients, 20 (4.1%) were current smokers, 92 (20.9%) had macromastia, and 51 (6.2%) breasts had a history of prior radiation. In the second half of the decade, patients were older (46.8 vs 44.7 years, p = 0.033), had larger BMIs (24.0 vs 22.8 kg/m2, p = 0.027), and a greater proportion had obesity (10.2% vs 3.2%, p = 0.004) and macromastia (23.8% vs 14.9%, p = 0.029; Table 1). There was no significant difference between the first and second halves of the decade in the proportion of active smokers (4.5% vs 3.9%, p = 0.758, respectively), patients with clinically-significant ptosis (33.3% vs 38.3%, p = 0.462), or breasts with a history of prior radiation (7.4% vs 5.7%, p = 0.389).

 

Conclusion: Over the last decade, indications for NSM have continued to expand to non-ideal patients. Our institution performed NSMs on a significantly increased proportion of women with larger breasts, higher BMIs, and older age throughout the last decade. 

05.07 An Analysis of Active surveillance as a Treatment Modality in Ductal Carcinoma in Situ

Posted on January 31, 2019

A. C. Alapati1, T. A. James1  1Beth Israel Deaconess Medical Center,Surgery,Boston, MA, USA

Introduction: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Current clinical trials are exploring active surveillance (AS) of DCIS. The purpose of this study is to characterize current practice trends in the use of AS.  The findings may inform clinical trials and provide insight into factors influencing adoption into practice.

Methods: The National Cancer Database was used to identify women diagnosed with DCIS from 2004-2015. Management with AS was defined as any patient not undergoing surgery, chemotherapy or radiation therapy. Multivariable logistic regression was used to assess patterns of AS.

Results: Of  84,281 women with DCIS, 342 (0.4%) underwent AS. Increased age, (OR 1.16), Hispanic/non-Hispanic black ethnicities (OR 1.90; 1.54), treatment at an academic facility (OR 1.76), non-private insurance (OR 1.29), lower grade (OR 1.34), and lower volume facilities (OR 1.60) were associated with higher use of AS. Patients with one or more comorbidities less frequently underwent AS compared with patients without morbidities. (OR 0.70) Residence distance from the treatment center showed no significance. Of all patients undergoing AS, 10.5% received hormonal therapy.

Conclusion: AS is currently an infrequently used treatment modality for patients with DCIS. We observed variations in AS based on age, ethnicity, facility type, facility volume, insurance status and tumor grade. The vast majority  of patients managed with AS did not receive hormone therapy. This information may further inform strategies for clinical trials, as well as quality of care in the management of DCIS.

 

05.06 Breast Density Does Not Differ Between Breast Cancer Receptor Subtypes

Posted on January 31, 2019

M. M. Goldbach1, D. I. Hoffman1, A. Malinovitch1, C. Huang1, M. Pomponio1, A. D. Williams1,3, S. M. Nazarian1, J. Tchou1,2  1Perelman School of Medicine at the University of Pennsylvania,Department Of Surgery,Philadelphia, PA, USA 2Perelman School of Medicine at the University of Pennsylvania,Abramson Cancer Center, Rena Rowan Breast Center,Philadelphia, PA, USA 3Lankenau Medical Center,Department Of Surgery,Wynnewood, PA, USA

Introduction:  Mammographic breast density (BD) is an established risk factor for breast cancer. The relationship between BD and breast cancer receptor subtype is unclear. We therefore aimed to evaluate differences in BD across tumor receptor subtypes at a large, academic medical center. Several studies have shown that triple negative breast cancers (TNBC) often present as interval breast cancer, i.e in between normal screening mammograms. We hypothesized that women with TNBC have denser breasts compared to women diagnosed with other breast cancer subtypes as classified by their hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression status.

Methods:  A retrospective database query from an institutional registry was performed to identify female patients diagnosed with primary breast cancer between 2009 – 2015 who also had a screening mammogram 6 ± 3 months prior to diagnosis at our institution. Patients were excluded if their breast cancers were noninvasive, metastatic at diagnosis, or had no receptor status information available. Patient demographic information, BD, and receptor status were collected. Categorical BD was measured using the Breast Imaging Reporting and Data System (BI-RADS) classification system (1 = almost entirely fatty, 2 = scattered fibroglandular densities, 3 = heterogeneously dense, 4 = extremely dense). A Chi-square test was performed to evaluate differences in BD across three tumor subtypes: HR+/HER2-, HER2+ (regardless of HR status), TNBC.  

Results: BD was assessed in 488 patients with invasive breast cancer. The cohort had a median age of 62 years (range 38 – 92). 58.2% of patients (284/488) were Caucasian, 37.9% (185/488) were Black, and 3.1% (15/488) were Asian. 78.5% of patients (383/488) had ER+/HER2- cancer, while 11.9% (58/488) had TNBC and 9.6% (47/488) had HER2+ cancer. The distributions of categorical BD between tumor receptor subtypes were summarized in Table 1. Overall, approximately 90% of patients (448/488) had a BI-RADS score of either 2 or 3. BD did not differ significantly across tumor receptor subtype (X2 2.88, p=0.823). 

Conclusion: In this pilot study, we report no significant difference in categorical breast density between breast cancer receptor subtypes. As categorical BD reporting is qualitative and has demonstrated inter- and intra-observer variability, we plan to quantify BD using our BD quantification software – Laboratory for Individualized Breast Radiodensity Assessment (LIBRA). We also plan to expand the cohort to increase our sample size. A multivariate logistic regression to control for other patient variables, including age, menopausal status, BMI, history of LCIS, and use of hormone replacement therapy is underway.

 

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