Eliminating Breast Surgery for Invasive Cancer with

Exceptional Response to Neoadjuvant Systemic

Therapy: Prospective Multicenter Clinical Trial
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Planned Initial Feasibility Endpoint

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Helen M Johnson, MD, Vicente Valero, MD, Wei T Yang, MBBS, MHM, Benjamin D Smith, MD,
Savitri Krishnamurthy, MD, Yu Shen, PhD, Heather Lin, PhD, Anthony Lucci, MD, FACS,
Gaiane M Rauch, MD, PhD, Henry M Kuerer, MD, PhD, FACS

BACKGROUND: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subse-
quent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic com-
plete response (pCR). The feasibility phase of the clinical trial reported here assesses omission
of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion.
STUDY DESIGN: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth
factor receptor 2-positive breast cancer (HER2+BC) cancer with <2 cm residual disease on post-
NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by
image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiother-
apy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recur-
rence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.
RESULTS: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8
years (range 51 to 75) and most patients were White (69.2%) and non-Hispanic/Latino
(84.6%). All patients had invasive ductal carcinoma (6 TNBC, 7 HER2+BC). Mean tumor
size was 2.4 cm (range 0.9 to 5.0) before NST and 0.7 cm (range 0 to 1.8) after NST. Seven
patients (53.8%) had residual disease identified on VACB; the remaining 6 (46.2%) com-
prised the feasibility cohort. At a median follow-up of 44.3 months (range 41.3 to 51.3) there
was no ipsilateral breast tumor recurrence in this cohort.
CONCLUSIONS: These early data suggest that omission of breast surgery in patients with invasive TNBC and
HER2+BC with no evidence of residual disease on standardized VACB after NST is poten-
tially feasible. Results from the expansion phase of this clinical trial will be reported per pro-
tocol prespecified analyses. (J Am Coll Surg 2023;237:101–108. © 2023 by the American
College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

CME questions for this article available at
http://jacscme.facs.org
Disclosure Information: Authors have nothing to disclose. Timothy
J Eberlein, Editor-in-Chief, has nothing to disclose. Ronald J Weigel,
CME Editor, has nothing to disclose.
Disclosures outside the scope of this work: Dr Yang receives royalty pay-
ments from Elsevier. Dr Smith receives salary support from Varian Medical
Systems and receives royalty payments and equity interest from Oncora
Medical. Dr Valero is a paid consultant to Hologic, Exact Science, Roche,
Novartis, and AstraZeneca. Dr Krishnamurthy is a paid scientific advisory
board member at AstraZeneca and is a paid consultant to Daichi Sankyo.
Support: Dr Kuerer is supported by the PH and Fay Etta Robinson
Distinguished Professorship in Cancer research and funding MD Anderson
Clinical Research Funding Award Program. Additional support provided by
a Cancer Center Support Grant (CA016672) from the National Institutes
of Health, which supports the Clinical Trials Support Unit and Biostatistics
Shared Resource, as well as a Clinical and Translational Science Award (grant
UL1 RR024148) to MD Anderson Cancer Center.
Presented at the Western Surgical Association 130th Scientific Session, Santa
Barbara, CA, November 2022.
Received December 19, 2022; Revised January 18, 2023; Accepted January
19, 2023.
From the Departments of Breast Surgical Oncology (Johnson, Lucci, Kuerer),
Breast Medical Oncology (Valero), Breast Imaging (Yang, Rauch), Radiation
Oncology (Smith), Pathology (Krishnamurthy), Biostatistics (Shen, Lin),
and Abdominal Imaging (Rauch), University of Texas MD Anderson Cancer
Center, Houston, TX.
Correspondence address: Henry M Kuerer, MD, PhD, FACS, Breast
Programs MD Anderson Cancer Network, University of Texas MD
Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1434, Houston,
Texas 77030-4009. email: hkuerer@mdanderson.org
A discussion of this article is available at http://links.lww.com/JACS/A274.

© 2023 by the American College of Surgeons. Published by Wolters Kluwer https://doi.org/10.1097/XCS.0000000000000670

Health, Inc. All rights reserved. 101 ISSN 1879-1190/22
 102 Johnson et al    Eliminating Breast Surgery Trial Feasibility
CONTINUING MEDICAL EDUCATION CREDIT INFORMATION
Accreditation
The American College of Surgeons is accredited by the Accreditation
Council for Continuing Medical Education (ACCME) to provide continuing
medical education for physicians.
AMA PRA Category 1 Credits™
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The American College of Surgeons designates this journal-based activity
for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should
claim only the credit commensurate with the extent of their participation
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in the activity.
Of the AMA PRA Category 1 Credits™ listed above, a maximum of 1.0
credits meet the requirements for Self-Assessment.
Abbreviations and Acronyms
DCIS = ductal carcinoma in situ
HER2+BC = human epidermal growth factor receptor 2-posi-
tive breast cancer
IBTR = ipsilateral breast tumor recurrence
NST = neoadjuvant systemic therapy
pCR = pathologic complete response
TNBC = triple-negative breast cancer
VACB = vacuum-assisted core biopsy
Neoadjuvant systemic therapy (NST) is frequently used in
the multimodality treatment of early-stage triple-negative
breast cancer (TNBC) and human epidermal growth fac-
tor receptor 2-positive breast cancer (HER2+BC).1 NST
facilitates less extensive breast and axillary surgery in cases
of substantive tumor downstaging and enables tailoring of
adjuvant therapies in cases of residual disease.2
Pathologic complete response (pCR) to NST is asso-
ciated with improved overall survival, event-free sur-
vival, and distant recurrence-free survival for TNBC and
HER2+BC.3,4 With modern systemic therapy for these
subtypes, pCR occurs in 46% to 68% of cases.5-8
Image-guided, vacuum-assisted core biopsy (VACB)
of the tumor bed after NST can accurately identify resid-
ual disease and predict pCR, with a false-negative rate
of approximately 3% when standardized techniques are
applied to highly selected patients.9,10 The ability to pre-
dict which breast cancers demonstrate pCR to NST in
the preoperative setting calls into question the relative
benefit of local therapy for these patients. This prospec-
tive multicenter clinical trial aims to evaluate the safety of
omitting breast surgery in women with invasive TNBC or
HER2+BC with exceptional response to NST.
The feasibility phase of the trial was designed to eval-
uate the safety of this new approach. If a local recurrence
J Am Coll Surg
occurred during the first 6 months after radiotherapy in the
6 patients demonstrated to have a breast pCR on image-
guided VACB, the data safety monitoring committee
would halt the protocol. In the absence of recurrence the
accrual would continue to 50 total patients in the expan-
sion phase of the trial with subsequent protocol-specified
planned outcome analyses. This article reports on the fea-
sibility phase of this prospective multicenter clinical trial
testing the safety of eliminating breast surgery among
patients with VACB-proven cases of pCR.
METHODS
Cohort selection
This prospective, multicenter, single-arm, phase-2
clinical trial was registered with the National Cancer
Institute (NCT02945579) and approved by the insti-
tutional review boards of all participating centers. All
patients provided informed consent. Women 40 years
of age or older with pathologically confirmed invasive,
unicentric, cT1-2 N0-1 M0 TNBC or HER2+BC with
less than 2 cm residual disease (mass, density, suspicious
calcifications, or enhancement) on post-NST imaging
were eligible to enroll. HER2+BC was defined as an
immunohistochemistry score of 3+ or amplified fluo-
rescence in situ hybridization. TNBC was defined by
estrogen receptor less than 10%, progesterone receptor
less than 10%, and HER2 immunohistochemistry of
1+ or 2+ or nonamplified fluorescence in-situ hybrid-
ization. Clinical stage was defined by mammography
and breast ultrasound including axillary nodal ultra-
sound and N1 was defined as 1 to 3 abnormal-appear-
ing nodes on ultrasound and pathologic confirmation
of metastatic disease on biopsy. MRI was performed
at physician discretion. Any NST regimen considered
standard for TNBC or HER2+BC was permissible. The
primary tumor was localized with image-guided clip
marker placement before initiation of NST. Exclusion
criteria included previous history of ipsilateral invasive
breast cancer or ductal carcinoma in situ (DCIS), preg-
nancy, and progression of disease during NST.
Trial design
The trial opened to accrual in March 2017. Patients
were eligible to enroll before, during, or after NST. At
enrollment, all patients were evaluated with a history
and physical examination. After completion of standard
NST, patients underwent mammography and ultrasound
of the breast and the axilla. The optimal modality for
image-guided biopsy of the breast tumor bed was deter-
mined by the operating radiologist. Image-guided VACB
 Vol. 237, No. 1, July 2023
was performed 2 to 6 weeks after completion of NST
and required 12 (at minimum) 9-gauge cores. Biopsy of
the previously placed clip was performed; the clip was
removed along with more than 90% of residual radiologic
abnormality if present in the tumor bed. A new clip was
placed at the biopsy site to facilitate localization in cases
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of residual disease and for ongoing imaging surveillance.
If residual invasive cancer or DCIS was identified on
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VACB pathology, patients were removed from the study
and proceeded to standard breast surgical therapy. If no
residual disease was identified, participants were eligible
to omit breast surgery and proceed to standard whole-
breast radiotherapy. Patients with cN1 disease were eligi-
ble to participate if they demonstrated a breast pCR on
VACB. They were required to undergo targeted axillary
dissection and completion axillary lymph node dissection
in the setting of residual nodal disease. Axillary surgery
was not required for patients with cN0 disease.
External beam radiotherapy was initiated within 12
weeks of NST completion. For cN0 patients, whole-breast
radiotherapy at a dose of 40.05 Gy in 15 fractions was
delivered, followed by a tumor bed boost at a dose of 14
Gy in 7 fractions. For cN1 patients, the radiation oncol-
ogist had the option to deliver whole-breast and regional
nodal radiation at a dose of 50 Gy in 25 fractions, followed
by the same boost. Patients were evaluated on a weekly
basis during radiotherapy. In the event of severe radiation
toxicity, the treating physician had the option to hold ther-
apy for up to 3 days, with substitution of tumor bed boost
for whole-breast therapy during this time, provided that
the total final doses met the previously mentioned criteria.
Figure 1. Flow diagram depicting progression of patients through the trial. HER2, human epidermal growth factor receptor 2.
Johnson et al    Eliminating Breast Surgery Trial Feasibility 103
Patients with HER2+BC completed adjuvant anti-HER2
targeted therapy, and hormone receptor-positive patients
also received adjuvant endocrine therapy.
After completion of radiotherapy, patients were evalu-
ated with a history and physical examination and mammo-
gram at 6-month intervals for 5 years. Abnormal radiologic
findings underwent additional imaging work-up or biopsy
to evaluate for tumor recurrence. Progression of patients
through the trial is illustrated in Figure 1.
Feasibility endpoint
The feasibility phase of the trial was designed to evalu-
ate 6 patients with no residual disease after NST, with a
primary endpoint of ipsilateral breast tumor recurrence
(IBTR). If any of the 6 patients in the feasibility cohort
experienced IBTR within 6 months of post-NST biopsy
demonstrating no residual disease, the study would be
halted, reviewed by principal investigators and the data
monitoring group, and either closed or modified. If no
IBTR were observed with this timeframe, patients in the
feasibility cohort would be rolled over to the expansion
cohort and continue in the second phase of the trial with
continued prespecified monitoring and outcome analyses
through 5 years of follow-up.
We chose a feasibility cohort sample size of 6 patients
for both practical consideration and statistical justification.
We intended to minimize the number of patients exposed
to a new treatment strategy with unknown outcome in
the event that IBTR rates were higher than with stand-
ard-of-care treatment. Additionally, we wanted to ensure
 104 Johnson et al    Eliminating Breast Surgery Trial Feasibility J Am Coll Surg

Table 1. Patient Characteristics Overall and by Presence or Absence of Residual Disease Identified After Neoadjuvant
Systemic Therapy on Image-Guided Vacuum-Assisted Core Biopsy
Residual disease No residual disease
Overall identified on VACB identified on VACB
Characteristic (n = 13) (n = 7) (n = 6)
Age, y, mean (range) 60.8 (51–75) 59.7 (52–67) 62.2 (51–75)
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Race, n (%)
 White 9 (69.2) 4 (57.1) 5 (83.3)
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 Black 3 (23.0) 2 (28.6) 1 (16.7)

 Asian 1 (7.7) 1 (14.3) 0
Ethnicity, n (%)
 Hispanic or Latino 2 (15.4) 1 (14.3) 1 (16.7)
 Non-Hispanic or Latino 11 (84.6) 6 (85.7) 5 (83.3)
Breast cancer subtype, n (%)
 Triple-negative 6 (46.2) 3 (42.9) 3 (50)
 HER2-positive 7 (53.8) 4 (57.1) 3 (50)
 Hormone receptor-positive 4 (30.8) 3 (42.9) 1 (16.7)
 Hormone receptor negative 3 (23.0) 1 (14.3) 2 (33.3)
Histology: invasive ductal carcinoma, n (%) 13 (100) 7 (100) 6 (100)
Grade, n (%)
 1 0 0 0
 2 5 (38.5) 2 (28.6) 3 (50)
 3 8 (61.5) 5 (71.4) 3 (50)
Tumor size, initial, cm, mean (range) 2.4 (0.9–5.0) 2.2 (0.9–3.1) 2.5 (1.2–5.0)
Tumor size, after NST, cm, mean (range) 0.7 (0–1.8) 1.1 (0.5–1.5) 0.3 (0–1.8)
Radiologic complete response, n (%) 5 (38.5) 0 5 (83.3)
No. of VACB cores, mean (range) 17.3 (12–30) 18.4 (12–30) 16 (12–24)
HER2, human epidermal growth factor receptor 2; NST, neoadjuvant systemic therapy; VACB, vacuum-assisted core biopsy.

the opportunity to progress to the expansion phase of the
study should IBTR rates prove similar to those seen with
standard breast surgical therapy. In a 6-patient cohort,
if the true IBTR rate at 6 months is 2%, the probabil-
ity of observing zero IBTR is 89% and the probability of
observing at least 1 IBTR is 11%. Alternatively, if the true
6-month IBTR rate is 15%, these probabilities are 38%
and 62%, respectively.
RESULTS
From March 2017 to October 2018, 13 patients were
enrolled, which led to 6 patients with pCR by VACB for
the feasibility cohort. Patient characteristics are shown in
Table 1. Overall, the median age was 62 years (range 51
to 75). Most patients were White (69%) and non-His-
panic/Latino (84%). All patients had either interme-
diate- (38.5%) or high-grade (61.5%) invasive ductal
carcinoma. Six patients had TNBC and 7 had HER2+BC.
All patients with TNBC were treated with adriamycin
and cyclophosphamide followed by paclitaxel. All patients
with HER2+BC were treated with docetaxel, carboplatin,
trastuzumab, and pertuzumab, except for 1 patient with
a 0.9-cm primary tumor who was treated with paclitaxel
and trastuzumab.
The median initial tumor size was 2.1 cm (range 0.9 to
5.0), which decreased to a median of 0.8 cm (range 0 to
1.8) after NST. The median number of VACB cores was
18 (range 12 to 30). Seven patients had residual disease
identified on VACB (4 with invasive cancer; 3 with DCIS
only). The remaining 6 patients comprised the feasibility
cohort.
Among the feasibility cohort, the median age was 62
years (range 51 to 75) and most women were White
(83%) or non-Hispanic/Latino (83%). Half of the cohort
had TNBC and were treated with adriamycin and cyclo-
phosphamide followed by paclitaxel, while the other half
had HER2+BC and were treated with docetaxel, carbo-
platin, trastuzumab, and pertuzumab. The median initial
tumor size was 2.1 cm (range 1.2 to 5.0). Five patients
(83.3%) had radiologically complete responses; the sixth
had a residual mass measuring 1.8 cm on post-NST imag-
ing. The median number of VACB cores was 15 (range 12
to 24).
 Vol. 237, No. 1, July 2023 Johnson et al    Eliminating Breast Surgery Trial Feasibility
Two patients with initial biopsy-proven N1 disease in
the feasibility cohort underwent planned targeted axillary
dissection per protocol, and no lymph node metastases
were identified. These patients with initial N1 disease were
treated with whole-breast and regional nodal radiotherapy
at a dose of 50 Gy in 25 fractions, whereas the other 4
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patients who did not present with N1 disease received 40
Gy in 15 fractions. All radiotherapy included a tumor bed
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boost per protocol criteria.
At a median follow-up of 44.3 months (range 41.3 to
51.3), there were no IBTRs in the feasibility cohort. At
6 months follow-up, 3 patients had mammograms with
abnormal results and were evaluated further with addi-
tional breast imaging. In 1 case, the mammogram noted
focal asymmetry in proximity to the biopsy clip; further
evaluation by ultrasound showed scarring and shadowing
consistent with postbiopsy changes. Contralateral breast
ultrasound was recommended for another patient because
of a sub-centimeter oval mass visualized on mammogram
that had the ultrasonographic appearance of fibrocystic
changes classified as Breast Imaging Reporting and Data
System category 2. A third patient’s mammogram report
noted postradiation changes at the site of the clip and
recommendation for ultrasound (read as “postradiation
changes limiting sonographic evaluation of the breast”), as
well as noting a stable benign mass in a different quadrant.
MRI was performed demonstrating suspicious nonmass
enhancement in the region of the benign-appearing mass
(seen on ultrasound) for which biopsy was recommended.
Ultrasound-guided biopsy was performed and pathology
demonstrated fibroadenoma with focal atypical lobular
hyperplasia.
At 12 months, 4 patients had benign mammographic
findings, including the patient who underwent 6-month
biopsy. One patient underwent stereotactic biopsy of a 0.9-
cm irregular mass associated with the biopsy clip attributa-
ble to increased interval size and pathology demonstrating
dense nodular stromal fibrosis. Another patient under-
went additional breast imaging because of mammographic
findings of focal asymmetry with indistinct margins which
preclude accurate size measurement. Ultrasound showed
postbiopsy changes classified as Breast Imaging Reporting
and Data System category 4A and MRI demonstrated a
correlative 1.5-cm irregular nonenhancing mass with spic-
ulated margins classified as Breast Imaging Reporting and
Data System category 4 with recommendation for biopsy.
Stereotactic biopsy was performed and pathology demon-
strated stromal fibrosis and therapy-related changes. This
patient underwent an additional stereotactic biopsy at 24
months for suspicious calcifications located in a different
quadrant than the tumor bed, with pathology demonstrat-
ing fibroadenoma with stromal calcifications.
105
Of note, 2 patients underwent surveillance ultrasound
in addition to mammogram in the absence of mam-
mographic abnormality per radiologist’s preference. One
of these patients was found to have 3 indeterminate,
sub-centimeter level 2 and 3 axillary lymph nodes at 48
months after radiation and underwent ultrasound-guided
biopsy which confirmed lymphoid tissue and was negative
for malignancy.
DISCUSSION
The results of the feasibility phase of this prospective mul-
ticenter clinical trial suggest the potential safety of omit-
ting breast surgery in patients with invasive TNBC and
HER2+BC with no evidence of residual disease using
standardized, image-guided VACB after NST. The feasi-
bility phase was planned because this was a high-risk and
high-potential impact trial where standard surgical ther-
apy has shown to be effective. None of the patients in the
feasibility cohort experienced an IBTR and therefore, the
trial was not halted and was allowed to reach accrual of 50
patients. Additionally, no feasibility cohort patient expe-
rienced IBTR at median 44.3-month follow-up (at time
of writing). This indicates potential very early oncologic
safety results for the de-escalation of local therapy in tum-
ors showing exceptional response to NST, demonstrated
by breast pCR on image-guided-VACB. This concept is
supported by the fact that definitive radiotherapy with-
out surgical resection—with or without systemic ther-
apy—has shown to be effective for selected patients with
esophageal, anal, laryngeal, prostate, cervical, or lung car-
cinoma.11 However, until recently, it was not possible to
accurately predict which patients with breast cancer were
free of residual disease after NST and could safely forego
surgery.12
NST is increasingly used for TNBC and HER2+BC.
In 2017, the St Gallen International Expert Consensus
panel strongly endorsed NST for stage II-III TNBC and
HER2+BC, especially for cases in which NST may facilitate
de-escalation of local therapy.1 Similarly, current National
Comprehensive Cancer Network guidelines recommend
NST for patients with operable TNBC and HER2+BC
in cases of cT2+ disease, cN1+ disease, or other cases for
which NST would enable breast conservation therapy or
less-extensive axillary surgery, as well as consideration for
NST for cT1cN0 disease.13 With advances in NST result-
ing in higher rates of pCR, the next logical step in the push
for de-escalation of surgical therapy is omission of breast
surgery for tumors with exceptional response to NST.
Higher rate of pCR may be expected in the future
as NST continues to be refined and new targeted ther-
apies, immunotherapies, and other novel agents are
 106 Johnson et al    Eliminating Breast Surgery Trial Feasibility
developed. Indeed, since the initiation of this trial, prac-
tice-changing trials such as Pembrolizumab (MK-3475)
Plus Chemotherapy vs Placebo Plus Chemotherapy as
Neoadjuvant Therapy and Pembrolizumab vs Placebo as
Adjuvant Therapy in Participants with Triple Negative
Breast Cancer (KEYNOTE-522) have been published,
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demonstrating improvements in pCR for TNBC (from
55% to 69%) with the addition of pembrolizumab to a
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standard chemotherapy backbone of NST.14 Studies are
ongoing to determine optimal NST and adjuvant sys-
temic therapy regimens for different stages of HER2+BC,
including possible de-escalation of standard cytotoxic
chemotherapy, with attention to pCR rates.2 As the pCR
rate continues to improve, if longer-term IBTR results
from the expansion phase of this trial support omission
of breast surgery in TNBC and HER2+BC with pCR to
NST, this concept will be tested in other subsequent pro-
spective trials and can potentially be offered to a greater
number of patients in the future.
Meticulous multidisciplinary patient selection is essen-
tial for the oncologic safety of breast surgery omission.
Preoperative identification of patients predicted to have
a pCR can be achieved with high accuracy by adhering
to standardized biopsy techniques. A false-negative rate of
less than 5% can be achieved through stringent patient
selection criteria, thorough sampling of the tumor bed
(including removal of the previously placed clip), use of
a larger-gauge VACB device with removal of multiple
cores, and meticulous specimen processing.9,10 The higher
false-negative rates reported in other studies (37-40%) can
be attributed to differences in selection criteria and biopsy
techniques.15,16 In this clinical trial, pCR was predicted
by examining a minimum of 12 cores with a single biopsy
procedure that used a 9G VACB device. This design was
informed by results of an earlier trial that demonstrated a
reduction in the rate of false negatives when using these
measures to ensure adequate tumor bed sampling.12 The
precision of this approach is further illustrated by the abil-
ity to discern both residual invasive disease and DCIS in
the 7 patients who were enrolled but did not meet criteria
for inclusion in the feasibility cohort, which is consistent
with previous reports of 95% sensitivity for residual dis-
ease.12 It is interesting to note that 1 patient in the feasi-
bility cohort did not have a radiologic complete response
to NST (ie with residual 1.8 cm on imaging) but did have
a pCR predicted by VACB. This is congruent with the
known variability in sensitivity and specificity of breast
imaging modalities for the detection of residual disease
after NST, as well as the described risk of radiologic over-
estimation of residual disease.11
This study is limited by several factors. First, the sam-
ple size of the initial feasibility cohort is very small. Given
J Am Coll Surg
the excellent locoregional recurrence-free survival rate of
patients with TNBC and HER2+BC who undergo NST
with pCR followed by breast-conservation therapy (98.6%
and 97.4% at 5 years, respectively),17 we anticipated a sim-
ilar rate in our feasibility cohort. Therefore, both a larger
number of patients and a longer median follow-up are nec-
essary to observe a single event of locoregional recurrence.
Five-year IBTR results from the expansion cohort will
provide key information. Early results from the expansion
cohort are very promising and demonstrate no detectable
IBTR at an approximate 2-year median follow-up for the
entire group of patients.18 Second, because of the nonzero
false-negative rate for predicting pCR by image-guided
VACB, it is possible that we failed to identify residual dis-
ease in some patients. While whole-breast radiotherapy
would be expected to effectively treat a small volume of
residual disease, it is possible that IBTR events could be
observed with a longer follow-up or larger cohort. Based
on the reported 5-year locoregional recurrence-free sur-
vival rate for patients with HER2+BC and TNBC (86.7%
and 89.9%, respectively) whose tumors did not demon-
strate pCR after NST and breast-conservation therapy,17
and assuming that a lower rate would be observed if sur-
gery were omitted, we anticipate at least 1 IBTR in the
expansion cohort of future reports (median follow-up 5
years) if the nonzero false-negative rate of VACB is clini-
cally meaningful.
CONCLUSIONS
In this high-risk and high-potential prospective clinical
trial, the feasibility cohort did not demonstrate any local
recurrence at 6 months per planned safety data monitor-
ing and no patient had recurrence at follow-up (median
44.3-months). The trial reached accrual of 50 patients and
subsequent outcomes will be reported per protocol-speci-
fied time-points. If these early limited results pan out, sev-
eral other prospective trials testing this novel approach will
be warranted in multiple medical settings.
Author Contributions
Data curation: Johnson, Yang, Smith, Krishnamurthy,
Lucci, Rauch
Visualization: Johnson
Writing – original draft: Johnson
Conceptualization: Valero, Yang, Smith, Rauch, Kuerer
Funding acquisition: Valero, Kuerer
Investigation: Valero, Yang, Smith, Krishnamurthy, Lucci,
Rauch, Kuerer
Methodology: Valero, Shen, Lin, Kuerer
Project administration: Valero, Kuerer
 Vol. 237, No. 1, July 2023
Resources: Valero, Kuerer
Supervision: Valero, Kuerer
Writing – review & editing: Valero, Yang, Smith,
Krishnamurthy, Shen, Lin, Lucci, Rauch, Kuerer
Formal analysis: Shen, Lin
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Acknowledgment: Exceptional Responders Study Group
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/22/2024
Participating Investigators: Emilia J Diego, MD, FACS,
Division of Breast Surgery, University of Pittsburgh Medical
Center Magee-Women’s Hospital, Pittsburgh, PA Judy C
Boughey, MD, FACS, Division of Breast and Melanoma
Surgical Oncology, Department of Surgery, Mayo Clinic,
Rochester, MN Richard L White, MD, FACS, Division
of Surgical Oncology, Department of Surgery, Carolinas
Medical Center, Levine Cancer Institute, Atrium Health,
Charlotte, NC Tanya W Moseley, MD, Department of
Breast Imaging, University of Texas MD Anderson Cancer
Center, Houston, TX Jessica WT Leung, MD, Department
of Breast Imaging, University of Texas MD Anderson Cancer
Center, Houston, TX Monica Huang, MD, Department
of Breast Imaging, University of Texas MD Anderson
Cancer Center, Houston, TX Rosalind P Candelaria,
MD, Department of Breast Imaging, University of Texas
MD Anderson Cancer Center, Houston, TX Beatriz E
Adrada, MD, Department of Breast Imaging, University
of Texas MD Anderson Cancer Center, Houston, TX Elsa
Arribas, MD, Department of Breast Imaging, University
of Texas MD Anderson Cancer Center, Houston, TX
Raquel FD van la Parra, MD, PhD, Department of Breast
Surgical Oncology, University of Texas MD Anderson
Cancer Center, Houston, TX Kelly K Hunt, MD, FACS,
Department of Breast Surgical Oncology, University of
Texas MD Anderson Cancer Center, Houston, TX Isabelle
Bedrosian, MD, FACS, Department of Breast Surgical
Oncology, University of Texas MD Anderson Cancer
Center, Houston, TX Mediget Teshome, MD, MPH,
FACS, Department of Breast Surgical Oncology, University
of Texas MD Anderson Cancer Center, Houston, TX
Susie X Sun, MD, MS, FACS, Department of Breast
Surgical Oncology, University of Texas MD Anderson
Cancer Center, Houston, TX Rosa F Hwang, MD, FACS,
Department of Breast Surgical Oncology, University
of Texas MD Anderson Cancer Center, Houston, TX
Makesha V Miggins, MD, FACS, Department of Breast
Surgical Oncology, University of Texas MD Anderson
Cancer Center, Houston, TX Matthew J Piotrowski, MD,
FACS, Department of Breast Surgical Oncology, University
of Texas MD Anderson Cancer Center, Houston, TX
Anna P Refinetti, MD, FACS, Department of Breast
Surgical Oncology, University of Texas MD Anderson
Cancer Center, Houston, TX Richard A Ehlers, MD,
Johnson et al    Eliminating Breast Surgery Trial Feasibility 107
FACS, Department of Breast Surgical Oncology, University
of Texas MD Anderson Cancer Center, Houston, TX.
Jessica Suarez Colen, MD, MPH, Department of Breast
Surgical Oncology, University of Texas MD Anderson
Cancer Center, Houston, TX Catherine E Loveland-Jones,
MD, MS, FACS, Division of Breast Surgery, MD Anderson
Cancer Center at Cooper University Health Care,
Camden, NJ Beth Ann Lesnikowski, MD, FACS, The
Breast Institute at JFK Medical Center, Atlantis, FL Laila
Samiian, MD, FACS, Section of Breast Surgical Oncology,
Baptist MD Anderson Cancer Center, Jacksonville, FL
Clayton D Chong, MD, Medical Oncology, The Queen’s
Health System, Honolulu, HI Simona F Shaitelman, MD,
EDM, Department of Radiation Oncology, University
of Texas MD Anderson Cancer Center, Houston, TX
Melissa P Mitchell, MD, PhD, Department of Radiation
Oncology, University of Texas MD Anderson Cancer
Center, Houston, TX.
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