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Incremental Cancer Detection of Locoregional Restaging with Diagnostic Mammography Combined with Whole-Breast and Regional Nodal Ultrasound in Women with Newly Diagnosed Breast Cancer

Rationale and Objectives

This study aims to determine if locoregional restaging with diagnostic mammography and ultrasound (US) of the whole breast and regional nodes performed for quality assurance in women with newly diagnosed breast cancer who were referred to a tertiary care center yields incremental cancer detection.

Materials and Methods

An institutional review board-approved retrospective, single-institution database review was performed on the first 1000 women referred to our center in 2010 with a provisional breast cancer diagnosis. Locoregional restaging consisted of diagnostic full-field digital mammography combined with US of the whole breast and regional nodal basins. Bilateral whole-breast US was performed in women with contralateral mammographic abnormality or had heterogeneously or extremely dense parenchyma. Demographic, clinical, and pathologic factors were analyzed.

Results

Final analyses included 401 women. Of the 401 women, 138 (34%) did not have their outside images available for review upon referral. The median age was 54 years (range 21–92); the median tumor size was 2.9 cm (range 0.6–18.0) for women whose disease was upstaged and 2.2 cm (range 0.4–15.0) for women whose disease was not upstaged. Incremental cancer detection rates were 15.5% (62 of 401) in the ipsilateral breast and 3.9% (6 of 154) in the contralateral breast ( P < 0.0001). The total upstage rate was 25% (100 of 401). Surgical management changed from segmentectomy to mastectomy in 12% (50 of 401). The re-excision rate after segmentectomy was 19% (35 of 189).

Conclusions

Locoregional restaging with diagnostic mammography combined with whole-breast and regional nodal US that is performed for standardization of the imaging workup for newly diagnosed breast cancer patients can reduce underestimation of disease burden and impact therapeutic planning.

Introduction

Locoregional staging of breast cancer is performed not only to determine the primary tumor size (T stage) and the regional nodal status (N stage), but also to identify additional foci of malignancy and to delineate the extent of disease to facilitate optimal treatment. The primary tumor size and the regional nodal status are important prognostic indicators. Neoadjuvant chemotherapy (NAC) is offered to women with node-positive or aggressive disease (ie, triple-negative or human epidermal growth factor receptor 2-positive [HER2+] subtypes) or large tumors. Defining the extent of the disease aids surgical planning and helps determine the appropriateness of breast-conserving surgery (BCS) vs mastectomy. The clinical N stage, which is based in part on imaging data, guides adjuvant radiation planning.

The standard of care for initial staging of breast cancer is imaging with mammography. The most common adjunct modalities to mammography are ultrasound (US) and magnetic resonance imaging (MRI). The use of breast US varies from whole breast to mammographic- or MRI-directed, targeted breast US. Additionally, the use of US to examine nodal basins has not been universally adopted. When regional nodes are examined using US, some centers evaluate only the axilla and other centers evaluate all regional nodal basins of the breast, including the axillary, infraclavicular, internal mammary, and supraclavicular regions. Despite reports in literature showing that MRI can identify additional disease in both the ipsilateral and contralateral breasts, the use of breast MRI for staging remains practice dependent . Controversy remains regarding benefits of preoperative breast MRI as measured by rates of re-excision, recurrence, and survival .

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Materials and Methods

Patient Selection

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Clinicopathologic Assessment

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On-Site Mammography Performed During Locoregional Restaging

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On-Site US Performed During Locoregional Restaging

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On-Site Imaging-Guided Biopsies Performed During Locoregional Restaging

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Retrospective Reinterpretation of Outside Images

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Surgical Management

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Data Analysis

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Institutional Review Board Statement

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Results

Patients and Imaging Procedures

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Characteristics Associated with Disease Upstaging

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Table 1

Locoregional Restaging by Age Group, Race or Ethnicity, Hormone Receptor Status, and Histopathology in 401 Women with Primary Breast Cancer

Variable No Change in Stage Upstaged_P_ Value n (%) n (%) Age group (y) 20–30 7(70) 3(30) >30–40 22(47) 25(53) >40–50 71(69) 32(31) >50–60 77(66) 40(34) 0.004 >60–70 53(71) 22(29) >70 41(84) 8(16) Race or ethnicity White 180(74) 64(26) African-American 32(54) 27(46) Asian 26(79) 7(21) 0.0006 Hispanic 28(50) 28(50) Other 5(56) 4(44) Hormone receptor status ER status ER− 40(54) 34(46) ER+ 189(68) 91(32) 0.02 ER status not evaluated \* 42(89) 5(11) HER2 status HER2− 205(68) 96(32) HER2+ 24(45) 29(55) 0.004 HER2 status not evaluated \* 42(89) 5(11) Histopathology DCIS 40(89) 5(11) IDC 124(65) 68(35) IDC/DCIS 82(67) 41(33) IDC/ILC 7(54) 6(46) 0.006 ILC/ALH, LCIS † 12(55) 10(46) Other ‡ 6(100) 0(0)

ALH, atypical lobular hyperplasia; DCIS, ductal carcinoma in situ; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LCIS, lobular carcinoma in situ.

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Positive Predictive Value of Biopsies

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Reassessment of Disease Extent on the Basis of Locoregional Restaging

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Table 2

Comparison of Disease Extent Based on OSF Reports and Locoregional Restaging at our Institution for 401 Women with Primary Breast Cancer ( P < 0.0001)

Extent of Disease After Locoregional Restaging Initial OSF U MF MC U, CL MF, CL MC, CL Extent of Disease n (%) n (%) n (%) n (%) n (%) n (%) U—350 women 290(83) 30(9) 24(7) 0(0) 2(0.6) 4(1) MF—26 women 0(0) 19(73) 7(27) 0(0) 0(0) 0(0) MC—22 women 0(0) 0(0) 22(100) 0(0) 0(0) 0(0) U, CL—2 women NA NA NA 1(50) 1(50) 0(0) MC, CL—1 woman NA NA NA 0(0) 0(0) 1(100)

CL, contralateral disease; MC, multicentric disease; MF, multifocal disease; OSF, outside imaging; U, unifocal disease.

Table 3

Incremental Cancer Detection Rates After Locoregional Restaging at Our Institution for 401 Women with Primary Breast Cancer \*

Incremental Cancer Detection Modality Ipsilateral Breast ( N = 401) Contralateral Breast ( N = 154)n (%)n (%) FFDM 10(2.5) 1(0.6) WBUS 37(9.2) 3(1.9) FFDM + WBUS 15(3.7) 2(1.3) Total 62(15.5) 6(3.9)

FFDM, full-field digital mammography; WBUS, whole-breast ultrasound.

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Reassessment of Surgical Plans on the Basis of Locoregional Restaging

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Reassessment of Disease Stage on the Basis of Locoregional Restaging

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Table 4

Comparison of N Stage ( P < 0.0001) and Disease Stage ( P < 0.0001) Identified by OSF and Locoregional Restaging at Our Institution for 401 Women with Primary Breast Cancer

N Stage After Locoregional Restaging Initial OSF Classification N0 N1 N2 N3 n (%) n (%) n (%) n (%) N0—357 women 274(76.8) 66(18.5) 1(0.3) 16(4.5) N1—42 women 0(0) 31(73.8) 1(2.4) 10(23.8) N2—1 woman 0(0) 0(0) 1(100) 0(0) N3—1 woman 0(0) 0(0) 0(0) 1(100)

Disease Stage After Locoregional Restaging Initial OSF Classification Stage 0 Stage I Stage II Stage III n (%) n (%) n (%) n (%) Stage 0—52 women 47(90.4) 1(1.9) 3(5.8) 1(1.9) Stage I—157 women 0(0) 95(60.5) 53(33.8) 9(5.7) Stage II—172 women 0(0) 2(1.2) 137(79.7) 33(19.2) Stage III—20 women 0(0) 0(0) 0(0) 20(100)

OSF, outside imaging.

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Discussion

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Conclusions

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Acknowledgment

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Appendix

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Table A1

Combinations of Outside Breast and Nodal Ultrasound Protocols for 401 Women with a Diagnosis of Primary Breast Cancer

Breast Ultrasound, n (%) Nodal Ultrasound, n (%) Axillary Region AX + IC + IM AX + IC + IM + SC Not Performed Total Bilateral targeted 5(1.2) 0(0) 1(0.2) 6(1.5) 12(3.0) Bilateral whole breast 88(21.9) 5(1.2) 8(2.0) 36(9.0) 137(34.2) Unilateral targeted 26(6.5) 1(0.2) 0(0) 85(21.2) 112(27.9) Unilateral whole breast 78(19.5) 2(0.5) 3(0.7) 35(8.7) 118(29.4) Not performed NA NA NA 22(5.5) 22(5.5) Total 197(49.1) 8(2.0) 12(3.0) 184(45.9) 401(100)

AX, axillary; IC, infraclavicular; IM, internal mammary; NA, not applicable; SC, supraclavicular.

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