What matters most: Randomized controlled trial of breast cancer surgery conversation aids across socioeconomic strata.

BACKGROUND: Women of lower socioeconomic status (SES) with early-stage breast cancer are more likely to report poorer physician-patient communication, lower satisfaction with surgery, lower involvement in decision making, and higher decision regret compared to women of higher SES. The objective of this study was to understand how to support women across socioeconomic strata in making breast cancer surgery choices. METHODS: We conducted a 3-arm (Option Grid, Picture Option Grid, and usual care), multisite, randomized controlled superiority trial with surgeon-level randomization. The Option Grid (text only) and Picture Option Grid (pictures plus text) conversation aids were evidence-based summaries of available breast cancer surgery options on paper. Decision quality (primary outcome), treatment choice, treatment intention, shared decision making (SDM), anxiety, quality of life, decision regret, and coordination of care were measured from T0 (pre-consultation) to T5 (1-year after surgery. RESULTS: Sixteen surgeons saw 571 of 622 consented patients. Patients in the Picture Option Grid arm (n = 248) had higher knowledge (immediately after the visit [T2] and 1 week after surgery or within 2 weeks of the first postoperative visit [T3]), an improved decision process (T2 and T3), lower decision regret (T3), and more SDM (observed and self-reported) compared to usual care (n = 257). Patients in the Option Grid arm (n = 66) had higher decision process scores (T2 and T3), better coordination of care (12 weeks after surgery or within 2 weeks of the second postoperative visit [T4]), and more observed SDM (during the surgical visit [T1]) compared to usual care arm. Subgroup analyses suggested that the Picture Option Grid had more impact among women of lower SES and health literacy. Neither intervention affected concordance, treatment choice, or anxiety. CONCLUSIONS: Paper-based conversation aids improved key outcomes over usual care. The Picture Option Grid had more impact among disadvantaged patients. LAY SUMMARY: The objective of this study was to understand how to help women with lower incomes or less formal education to make breast cancer surgery choices. Compared with usual care, a conversation aid with pictures and text led to higher knowledge. It improved the decision process and shared decision making (SDM) and lowered decision regret. A text-only conversation aid led to an improved decision process, more coordinated care, and higher SDM compared to usual care. The conversation aid with pictures was more helpful for women with lower income or less formal education. Conversation aids with pictures and text helped women make better breast cancer surgery choices.

Encapsulated papillary carcinoma with and without frank invasion: Comparison of clinicopathologic features and role of axillary staging.

To investigate clinical and pathologic features of encapsulated papillary carcinomas (EPCs) that may be associated with invasive disease and characterize the axillary staging practices for EPCs at our institution. A pathology database search for cases containing "papillary carcinoma" was performed. Slides were reviewed by two pathologists. Clinicopathological features and axillary staging practices of EPCs with and without invasion were compared. Twenty-five cases of EPCs were identified. Fifteen cases contained a frank invasive tumor (60%), which were all pT1 (0.7 ± 0.56 cm), and the majority were ER-positive, HER2-negative, low-grade IDC-NST. Seventeen patients underwent sentinel lymph node biopsies (SLNB). No nodal metastases were identified. Follow-up was available for 24 patients (mean = 39 ± 29 months); 23 had no NED. Patients that presented with a self-palpated mass (versus screening) were more likely to have an invasive component; however, no pathologic or radiologic features differentiated EPCs with and without frank invasion. Pathologic and radiologic characteristics did not differentiate EPCs with and without frank invasion. EPCs have an excellent prognosis supported by the notable disease-free survival and negative nodal status in our cohort, which supports the notion that patients with EPCs may forgo axillary staging.

The shape of breast cancer.

PURPOSE: Little is known about the three-dimensional shape of breast cancer. Implicit to approaches that localize the center of the tumor for breast-conserving surgery (BCS) of non-palpable cancers is the assumption that breast cancers are spherical about a central point, which may not be accurate. METHODS: Pre-operative supine breast MRI images were obtained of 83 breast cancer patients undergoing partial mastectomy using supine MRI-guided resection techniques. Three-dimensional (3D) tumor models were derived after radiologists outlined tumor edges on successive MRI slices. Ideal resection volumes were determined by adding 1 cm in every dimension to the actual tumor volume. Geometrically defined parameters were used to define tumor shapes and associations between clinical variables and shapes were examined. RESULTS: Seventy-five patients had invasive cancer. Breast cancers were categorized into four tumor shapes: 34% of tumors were discoidal, 29% segmental, 19% spherical, and 18% irregular. If hypothetical spherical excisions were performed, non-spherical cases would excise 143% more tissue than the ideal resection volume. When the 3D shape of each tumor was provided to the surgeon during MR-guided BCS, the percentage of tissue overexcised in non-spherical cases was significantly less (143% vs. 66%, p < 0.001). CONCLUSIONS: Information obtained from a supine MRI can be used to generate 3D tumor models and rapidly classify breast tumor shapes. The vast majority of invasive cancers and DCIS are not spherical. Knowledge of tumor shape may allow surgeons to excise breast cancer more precisely.

Cosmetic Outcomes Following Breast-Conservation Surgery and Radiation for Multiple Ipsilateral Breast Cancer: Data from the Alliance Z11102 Study.

BACKGROUND: Diagnoses of multiple ipsilateral breast cancer (MIBC) are increasing. Historically, the primary treatment for MIBC has been mastectomy due to concerns about in-breast recurrence risk and poor cosmetic outcome. The Alliance Z11102 study prospectively assessed cosmetic outcomes in women with MIBC treated with breast-conserving therapy (BCT). PATIENTS AND METHODS: Z11102 was a multicenter trial enrolling women with two or three separate sites of biopsy-proven malignancy separated by ≥ 2 cm within the same breast. Cosmetic outcome was a planned secondary endpoint. Data were collected with a four-point cosmesis survey (1 = excellent, 4 = poor) and the BREAST-Q (scored 0-100). All patients undergoing successful breast-conserving therapy were treated with whole-breast radiation. Associations were assessed with Chi square or Fisher's exact tests as appropriate. RESULTS: Cosmetic outcome data for 216 eligible women who completed therapy are included in this analysis. Of the 136 patients who completed the survey 2 years postoperatively, 70.6% (N = 96) felt the result was good or excellent, while 3.7% (N = 5) felt the result was poor. We found no significant differences in patient-reported cosmetic outcomes when stratifying by patient age, number of lesions (two or three), number of incisions, number of lumpectomies, or size of largest area of disease. Mean satisfaction score on the BREAST-Q was 77.2 at 6 months following whole-breast radiation and 73.7 at 3 years following surgery. CONCLUSIONS: BCT performed for MIBC results in good or excellent cosmesis for the majority of women. From a cosmetic perspective, BCT is a valid surgical approach to women with MIBC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01556243.

Screening vs staging magnetic resonance imaging-guided core needle breast biopsies: Does MRI indication impact upgrade rate?

Adjunct magnetic resonance imaging (MRI) for both screening high-risk patients and staging for patients with newly diagnosed breast cancer leads to an increased number of biopsies and increased detection of atypical lesions. We assessed whether the malignancy upgrade frequency for high-risk atypia identified via MRI-guided biopsies varied based on indication: high-risk screening vs staging for malignancy. Among 399 MRI-guided biopsies, 46 (11.5%) high-risk lesions (ADH, ALH, and LCIS) were identified. Surgical excision was performed on 37% of 46%, and 24.3% were upgraded to invasive malignancy or DCIS. Of lesions identified by staging MRI, a slightly higher percentage, 28.5%, were upgraded (P = .36). Our data suggest that surgeons should carefully consider excisional biopsy for atypia identified on MRI regardless of indication.

A Randomized Prospective Trial of Supine MRI-Guided Versus Wire-Localized Lumpectomy for Breast Cancer.

BACKGROUND: Wire-localized excision of non-palpable breast cancer is imprecise, resulting in positive margins 15-35% of the time. METHODS: Women with a confirmed diagnosis of non-palpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) were randomized to a new technique using preoperative supine magnetic resonance imaging (MRI) with intraoperative optical scanning and tracking (MRI group) or wire-localized (WL group) partial mastectomy. The main outcome measure was the positive margin rate. RESULTS: In this study, 138 patients were randomly assigned. Sixty-six percent had IBC and DCIS, 22% had IBC, and 12% had DCIS. There were no differences in patient or tumor characteristics between the groups. The proportion of patients with positive margins in the MRI-guided surgery group was half that observed in the WL group (12 vs. 23%; p = 0.08). The specimen volumes in the MRI and WL groups did not differ significantly (74 ± 33.9 mL vs. 69.8 ± 25.1 mL; p = 0.45). The pathologic tumor diameters were underestimated by 2 cm or more in 4% of the cases by MRI and in 9% of the cases by mammography. Positive margins were observed in 68% and 58% of the cases underestimated by 2 cm or more using MRI and mammography, respectively, and in 15% and 14% of the cases not underestimated using MRI and mammography, respectively. CONCLUSIONS: A novel system using supine MRI images co-registered with intraoperative optical scanning and tracking enabled tumors to be resected with a trend toward a lower positive margin rate compared with wire-localized partial mastectomy. Margin positivity was more likely when imaging underestimated pathologic tumor size.

Papillary and sclerosing lesions of the breast detected and biopsied by MRI: Clinical management, upgrade rate, and association with apocrine metaplasia.

Benign papillary and sclerosing lesions of the breast (intraductal papillomas, complex sclerosing lesions, radial scars) are considered high-risk lesions due to the potential for upgrade to carcinoma on subsequent surgical excision. Optimal clinical management of such lesions remains unclear due to variable reported upgrade rates. Apocrine metaplasia is a common finding in breast tissue and its role in MRI enhancing lesions is increasingly being recognized. The purpose of this study was to investigate the MRI features of papillary and sclerosing lesions of the breast, evaluate the clinical management and upgrade rate of such lesions, and examine the contribution of apocrine metaplasia to the imaging findings. A 13-year retrospective review of MRI-guided biopsies identified 70 MRI-detected and -biopsied papillary and sclerosing lesions. Sixteen lesions without atypia underwent surgical excision; only one case (6%) was upgraded to pleomorphic lobular carcinoma in situ. The majority (64%) of biopsies contained apocrine metaplasia either within or adjacent to the targeted lesion. We found that half of MRI-detected lesions had T2 hyperintense foci (2-5 mm) or masses (>5 mm) adjacent to the lesion. Histologic correlation showed apocrine cysts were likely responsible for this imaging finding in 56% of these cases.

The Feasibility of Breast-Conserving Surgery for Multiple Ipsilateral Breast Cancer: An Initial Report from ACOSOG Z11102 (Alliance) Trial.

BACKGROUND: Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-conserving therapy (BCT). We report the feasibility of BCT in MIBC from the ACOSOG Z11102 trial [Alliance], a single arm noninferiority trial of BCT for women with two or three sites of malignancy in the ipsilateral breast. METHODS: Women who enrolled preoperatively in ACOSOG Z11102 were evaluated for conversion to mastectomy and need for reoperation to obtain negative margins. Characteristics of women who successfully underwent BCT and those who converted to mastectomy were compared. Factors were examined for association with the need for margin reexcision. RESULTS: Of 198 patients enrolled preoperatively, 190 (96%) had 2 foci of disease. Median size of the largest tumor focus was 1.5 (range 0.1-7.0) cm; 49 patients (24.8%) had positive nodes. There were 14 women who underwent mastectomy due to positive margins, resulting in a conversion to mastectomy rate of 7.1% (95% confidence interval [CI] 3.9-10.6%). Of 184 patients who successfully completed BCT, 134 completed this in a single operation. Multivariable logistic regression analysis did not identify any factors significantly associated with conversion to mastectomy or need for margin reexcision. CONCLUSIONS: Breast conservation is feasible in MIBC with 67.6% of patients achieving a margin-negative excision in a single operation and 7.1% of patients requiring conversion to mastectomy due to positive margins. No characteristic was identified that significantly altered the risk of conversion to mastectomy or need for reexcision. CLINICALTRIALS. GOV IDENTIFIER: NCT01556243.

What matters most: protocol for a randomized controlled trial of breast cancer surgery encounter decision aids across socioeconomic strata.

BACKGROUND: Breast cancer is the most commonly diagnosed malignancy in women. Mastectomy and breast-conserving surgery (BCS) have equivalent survival for early stage breast cancer. However, each surgery has different benefits and harms that women may value differently. Women of lower socioeconomic status (SES) diagnosed with early stage breast cancer are more likely to experience poorer doctor-patient communication, lower satisfaction with surgery and decision-making, and higher decision regret compared to women of higher SES. They often play a more passive role in decision-making and are less likely to undergo BCS. Our aim is to understand how best to support women of lower SES in making decisions about early stage breast cancer treatments and to reduce disparities in decision quality across socioeconomic strata. METHODS: We will conduct a three-arm, multi-site randomized controlled superiority trial with stratification by SES and clinician-level randomization. At four large cancer centers in the United States, 1100 patients (half higher SES and half lower SES) will be randomized to: (1) Option Grid, (2) Picture Option Grid, or (3) usual care. Interviews, field-notes, and observations will be used to explore strategies that promote the interventions' sustained use and dissemination. Community-Based Participatory Research will be used throughout. We will include women aged at least 18 years of age with a confirmed diagnosis of early stage breast cancer (I to IIIA) from both higher and lower SES, provided they speak English, Spanish, or Mandarin Chinese. Our primary outcome measure is the 16-item validated Decision Quality Instrument. We will use a regression framework, mediation analyses, and multiple informants analysis. Heterogeneity of treatment effects analyses for SES, age, ethnicity, race, literacy, language, and study site will be performed. DISCUSSION: Currently, women of lower SES are more likely to make treatment decisions based on incomplete or uninformed preferences, potentially leading to poorer decision quality, quality of life, and decision regret. This study hopes to identify solutions that effectively improve patient-centered care across socioeconomic strata and reduce disparities in decision and care quality. TRIAL REGISTRATION: NCT03136367 at ClinicalTrials.gov Protocol version: Manuscript based on study protocol version 2.2, 7 November 2017.

Relationship of breast MRI to recurrence rates in patients undergoing breast-conservation treatment.

PURPOSE: The effect of pre-operative MRI on the in-breast tumor recurrence rate (IBTR) of patients undergoing breast-conservation treatment (BCT) remains uncertain. We began to routinely perform pre-operative MRI in 2006. Our goal was to determine the effect of pre-operative MRI on IBTR. METHODS: Retrospective review of a prospective database of all patients undergoing BCT (n = 1396) from 2000 to 2010. IBTR were calculated using Kaplan-Meier estimates. RESULTS: 664 (47.6%) patients underwent pre-operative MRI. The use of MRI increased from 13.9% in 2000-2005 to 80.7% in 2006-2010. Ten percent of patients who underwent MRI were found to have an additional ipsilateral cancer, with a mean diameter of 1.6 cm. The IBTR for patients with and without MRI were 4% vs. 8% at 8 years (p = 0.04). In multivariate analysis, radiation therapy and endocrine therapy were associated with decreased IBTR, but MRI was not (RR 0.77 (0.45-1.28)). For 1030 patients with invasive cancer, the IBTR at 8 years with and without MRI was 4.2% vs. 7.3% (p = 0.28). For 366 DCIS patients with and without MRI, the IBTR was 3.6% vs. 10.9% (p = 0.06). In the subgroup of DCIS patients who did not receive radiation, the IBTR with and without MRI was 0% vs. 18.2% (p = 0.08). Patients with an additional cancer found by MRI had a higher IBTR at 8 years (10.1% vs. 3.3%, p = 0.02). CONCLUSIONS: In a study analyzing BCT patients from one time period who rarely had a pre-operative MRI and a subsequent time period where most patients had MRI, the use of MRI was associated with a decrease in the IBTR on univariate, but not multivariate analysis. Patients who had additional cancers detected had a significantly higher IBTR.

Reviewing the Evidence to Guide Clinical Care: Proliferative Breast Lesions in Breast Reduction Specimens.

The number of reduction mammoplasties performed in the United States continues to increase annually. Given the high incidence of breast cancer in women, it is routine practice for breast tissue excised during routine breast reductions procedures to be sent for pathology review. During pathology assessment, occult malignancy and on-occasion proliferative breast lesions of unknown and/or variable malignancy may also be present. We provide a review of commonly diagnosed atypical proliferative breast lesions in breast reduction specimens and a guide to plastic surgeons for further management.

Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005­December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

The PI3K/mTOR dual inhibitor P7170 demonstrates potent activity against endocrine-sensitive and endocrine-resistant ER+ breast cancer.

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway has been implicated in anti-estrogen resistance in breast cancer. We tested the therapeutic potential of the novel PI3K/mTOR dual inhibitor P7170 in a panel of anti-estrogen-sensitive and anti-estrogen-resistant models of ER+ breast cancer. Estrogen receptor-positive (ER+) breast cancer cells were treated ±P7170. Fresh cores from primary ER+/HER2- tumors from two patients were treated ±P7170 ex vivo. Mice bearing breast cancer xenografts were randomized to treatment with vehicle, fulvestrant, P7170, or combinations, and tumor volumes were measured. Tissues and cells were analyzed for markers of pathway activity, cell viability, and apoptosis. In cell lines, P7170 exhibited IC50 values in the range of 0.9-7 nM and induced apoptosis. P7170 potently inhibited mTOR activity (≤ 25 nM) and inhibited PI3K at higher concentrations (≥ 200 nM). P7170 completely inhibited MCF-7 tumor growth, significantly inhibited growth of fulvestrant-resistant T47D tumors, and suppressed tumor cell proliferation but did not induce apoptosis. While P7170 inhibits PI3K and mTOR in ER+/HER2- human breast cancer cells and tumors ex vivo, in vivo data indicate that the primary mechanism of P7170 anti-tumor action is inhibition of mTOR and cell proliferation. P7170 is a novel agent worthy of further investigation for the treatment of ER+ breast cancer.

Early postoperative outcomes in lumpectomy versus simple mastectomy.

BACKGROUND: Relatively scarce outcomes research exists that compares early postoperative complications between breast conservation surgery (BCS) and simple mastectomy (SM). Such information would improve a surgeon's ability to provide informed consent when considering treatment options, especially for women with early stage breast cancer who have the option to receive either BCS or SM. MATERIALS AND METHODS: The National Surgical Quality Improvement Program database from years 2009-2012 was analyzed. For each treatment group, we used Current Procedural Terminology codes specific to the treatment modality with sentinel lymph node biopsy as an inclusion criteria. We excluded patients who received axillary lymphadenectomies, bilateral disease or symmetry procedures, and additional breast reconstructive surgery. We compared each group with chi square and two-sample t-tests to look for preoperative comorbidity differences, then used unadjusted odds ratios to compare postoperative complication rates. RESULTS: Inclusion and exclusion criteria provided 6682 patients in the BCS group and 3339 patients in the SM group. Baseline comorbid condition characteristics showed no clinical differences between groups except for diabetes (8.5% in SM versus 6.5% in BCS). Statistical analysis between each treatment modality revealed that the SM group had significantly higher wound complications, bleeding, infections, and overall complications than the BCS group. CONCLUSIONS: Although both BCS and SM options have low early postoperative complication rates when treating early stage breast cancer, BCS has fewer complications with regard to bleeding, wound complications and infections.