QUANTITATIVE SURVEY

PATHOLOGISTS

Programming instructions are noted in BLUE BOLDED text

[For Recruiter] Background for Recruitment

We are conducting a research study to develop an understanding of pathologists’ current awareness of

HER2-low in the context of breast cancer and other cancer types across global markets. The survey will
particularly explore changes to the following topics as treatment options emerge:

 Awareness of HER2-low and perceived HER2-low prevalence

 Awareness of recent events (e.g., ASCO conference, NEJM publication, CAP guidelines)
 Current testing and reporting practices of HER2-low

We are looking to recruit 320 respondents with the following breakdown by geography:

Market US CA DE UK FR IT SP BR JP CN
Sample 50 30 30 30 30 30 30 30 30 30

The survey is aimed at being 10 minutes long and hosted online.

_____________________________________________________________________________________
Privacy, Confidentiality, and Code of Conduct

Please note that the aim of this market research study is solely to gain your views and is not in any way
promotional. Participation is entirely voluntary, and you have the right to withhold information or to
withdraw from the interview at any time. Your information will only be used for the purpose of this
market research study and will not be passed to any other organization without your permission.

We would also like to reassure you that:

1. [IF DE, ES, FR, IT] We will comply with the European General Data Protection Regulation
Practical Guide (GDPR) and all of your country’s applicable Data Protection laws and regulations.
Additionally, in accordance with GDPR, we are required to reveal the names of all entities
defined as “Data Controllers”. For this study, the marketing research agency and the data
collection company that recruited you are considered Data Controllers.
2. [IF DE, ES, FR, IT] We work in accordance with the European Pharmaceutical Marketing Research
Association (EphMRA) guidelines and the European Society for Opinion and Marketing Research
(ESOMAR) codes of conduct.
3. [IF UK] The research will comply with European data protection laws and is carried out within
the codes of conduct of the Market Research Society, EphMRA and the British Healthcare
Business Intelligence Association’s Legal & Ethical Guidelines.

1
 4. [For DE and FR] Finally, As I am sure you are aware, public officials should let their employers
know that they will perform activities for private companies and obtain their prior written
consent, in order to participate in market research studies and be remunerated for this. If you
are employed in a public entity, could you please confirm that you have obtained a written
consent from your employer?
5. [For FR only] Finally, the study will be conducted in accordance with the Loi Bertrand including
anti-gift laws. This meeting will be a "Market Research" agreement between Bionest and
yourself. Pursuant to decree no. 2020-730 of June 15, 2020 relating to benefits offered by
persons manufacturing or marketing healthcare products or services, and the order of August 7,
2020 setting the amounts above which an agreement provided for in article L.1453-8 of the
French public health code and stipulating the granting of benefits is subject to authorization,
your agreement will be transmitted by teleprocedure, by Bionest, no later than eight working
days before the benefit is granted to the national council of the order concerned. Under the
French rules on transparency:
o The information in this agreement includes: your contact details (name, surname),
professional specialty and qualifications, work address, RPPS, details, the subject of the
agreement (Market Research), the issue date of honorarium payment (the honoraria
amount will not be released), and any hospitality expenses (e.g., meals).
o This information will be processed automatically and will be published on the public
website: https://www.entreprisestransparence.sante.gouv.fr.
o You can access your personal information and have it corrected by contacting Bionest.
6. [For CN only] The research will comply with the China cross-board data transfer law and
regulations for your consent.

Adverse Event Reporting

We are required to pass on to our client details of adverse events, drug exposed pregnancies, and / or
product complaints that are mentioned during the course of market research interviews. Although this is
market research and the insights you provide will, of course, be treated in confidence, should you raise
during the market research an adverse event, a case of drug exposed pregnancy, and /or a product
complaint, we will need to report this even if it has already been reported by you directly to the
company and/or the regulatory authorities. [DO NOT SHOW FOR DE] In such a situation you will be
asked whether or not you are willing to waive the confidentiality given to you under the Market
Research Codes of Conduct specifically in relation to that adverse event/drug exposed
pregnancy/product complaint.

Are you happy to participate with the survey on this basis?

1. I agree CONTINUE
2. I do not agree TERMINATE

Before we start, I want to let you know that we keep all names confidential. We will group your
comments with those of other respondents, so please feel free to be candid in your responses.

2
Note to Programmer: When a question has “Other” as an option, please do not show that they must
write a response until after they select that answer so not to bias them toward strictly multiple-choice
questions. This is noted as [WAIT].
Please also program in a progress bar to show current completion rate of survey.

SCREENER QUESTIONS FOR PATHOLOGISTS

[ALLOW PARTICIPANTS TO COMPLETE SURVEY ONLY IF THEY PASS THE SCREENER]

INTRODUCTION

Hello, and thank you for participating. This study is being conducted to develop an understanding of
pathologists’ current awareness, testing, and reporting of low levels of HER2 expression in the context of
breast cancer across global markets.

We will begin this process by asking you a few questions to verify your qualification for participating in
the survey.

S1. Please indicate the country in which you practice. Select one [SINGLE CHOICE, CLOSED-END]

A. United States
B. Canada
C. United Kingdom
D. Germany
E. France
F. Italy
G. Spain
H. Brazil
I. Japan
J. China
K Other [TERMINATE]

S2. Please indicate your primary medical specialty. Select one [SINGLE CHOICE, CLOSED-END]

A. Pathology
B. Other [TERMINATE]

3
S3. [FOR US RESPONDENTS] Are you currently board-certified? Select one [SINGLE CHOICE,
CLOSED-END]
A. Yes
B. No [TERMINATE]

S4. What is your role within the lab? Select one [SINGLE CHOICE, CLOSED-END]

A. Head of Pathology
B. Lab Director
C. Molecular Pathologist
D. Anatomical/Clinical Pathologist
E. Histopathologist
F. Cytopathologist
G. Biomedical Scientist
H. Lab Technician [TERMINATE]

S5. How many years have you been in practice? Provide your response below [2 DIGIT, NUMERIC]

[XX] Years [TERMINATE IF <2 OR >35]

S6. Which of the following best describes the setting in which you primarily practice? Select one
[SINGLE CHOICE, CLOSED-END]
A. University / Academic Hospital
B. Cancer Center
C. General / District Hospital
D. Community-based Practice
E. Reference Lab
F. Private Laboratory / Private Practice
G. Other [TERMINATE]

S7. Does your lab perform HER2 immunochemistry (IHC) testing in-house or send out? Select one
[SINGLE CHOICE, CLOSED-END]

4
 A. Perform: in-house; Interpret: in-house

B. Perform: send out; Interpret: in-house

C. Perform: in-house; Interpret: send out [TERMINATE]

D. Perform: send out; Interpret: send out [TERMINATE]

S8. In an average 12-month timespan, how many breast cancer specimens come through your lab
as part of the diagnostic process? Provide your response below [1-5 DIGIT NUMERIC]
[XXX] breast cancer specimens

MAIN SURVEY
Section 1: Current HER2 Testing, Scoring, and Reporting Practices

Thank you for answering our initial questions. You have qualified to take part in the main portion of our
survey. We will begin by asking questions around your current practice setting and HER2 testing
practices, including the current testing rates at your practice.
SHOW ON NEW SCREEN

1. For the following tumor types listed below, please estimate the percentage of specimens that
undergo HER2 testing. [1-3 DIGIT NUMERIC]
[XXX] % of breast cancer specimens
[XXX] % of gastric cancer specimens
[XXX] % of colorectal cancer specimens
[XXX] % lung cancer specimens
[XXX] % of endometrial/uterine cancer specimens
[XXX] % of bladder cancer specimens

2. Which immunohistochemistry (IHC) assay(s) do you use for HER2 testing in breast cancer?
Please select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. PATHWAY anti-HER2/neu (4B5) (Rabbit monoclonal; FDA, CE-IVD, Roche)
B. [EXCLUDE FOR US] VENTANA anti-HER2/neu (4B5) (Rabbit monoclonal; CE-IVD, Roche)
C. HercepTest for Dako Autostainer (Rabbit polyclonal; Dako/Agilent)
D. HercepTest mAb pharmDx DG44 (rabbit monoclonal; Dako/Agilent)

5
E. Bond Oracle HER2 IHC system CB11 (Mouse monoclonal; Leica Biosystems)
F. Lab-developed test using 4B5 (Rabbit polyclonal; Roche)
G. Lab-developed test using A0485 (Rabbit polyclonal; Dako/Agilent)
H. Lab-developed test using 10A7 (Mouse monoclonal; Leica Biosystems)
I. Lab-developed test using EP3 (Rabbit monoclonal; Cell Marque/Epitomics/Zytomed)
J. Lab-developed test using SP3 (Rabbit monoclonal; Cell Marque/Thermo Fisher/Zytomed)
K. I do not know
Other - Assay / Platform [WAIT] (Please specify) [IF OTHER IS SELECTED, PARTICIPANTS MUST
L.
SPECIFY IN ORDER TO PROCEED TO NEXT QUESTION]

3. Do you use the same immunohistochemistry (IHC) assay(s) for HER2 testing in other tumor
types? Please select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. I use the same assay as I do for breast cancer
B. I use a different assay for other tumor types

4. [IF RESPONDENT SELECTED ‘B’ IN QUESTION 3] Which immunohistochemistry (IHC) assay(s) do

you use for HER2 testing in other tumor types? Please select all that apply [MULTIPLE CHOICE,
CLOSED-END]
A. PATHWAY anti-HER2/neu (4B5) (Rabbit Monoclonal; FDA, CE-IVD, Roche)
[EXCLUDE FOR US RESPONDENTS] VENTANA anti-HER2/neu (4B5) (Rabbit Monoclonal; CE-IVD,
B.
Roche)
C. HercepTest for Dako Autostainer (Rabbit polyclonal; Dako/Agilent)
D. HercepTest mAb pharmDx DG44 (rabbit monoclonal; Dako/Agilent)
E. Bond Oracle HER2 IHC system CB11 (Mouse monoclonal; Leica Biosystems)
F. Lab-developed test using 4B5 (Rabbit polyclonal; Roche)
G. Lab-developed test using A0485 (Rabbit polyclonal; Dako/Agilent)
H. Lab-developed test using 10A7 (Mouse monoclonal; Leica Biosystems)
I. Lab-developed test using EP3 (Rabbit monoclonal; Cell Marque/Epitomics/Zytomed)
J. Lab-developed test using SP3 (Rabbit monoclonal; Cell Marque/Thermo Fisher/Zytomed)
K. I do not know
L. Other - Assay / Platform [WAIT] (Please specify) [IF OTHER IS SELECTED, PARTICIPANTS MUST

6
 SPECIFY IN ORDER TO PROCEED TO NEXT QUESTION]

5. What autostainer(s) do you use in your lab? Please select all that apply [MULTIPLE CHOICE,
CLOSED-END]
A. Ventana Benchmark Ultra
B. Ventana Benchmark XT
C. Ventana Benchmark GX
D. Leica Bond III
E. Leica Bond Max
F. Dako Autostainer Plus
G. Dako Link 48
H. Dako Omnis
I. I do not know
Other [WAIT] (Please specify) [IF OTHER IS SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER
J.
TO PROCEED TO NEXT QUESTION]

6. Which elements related to scoring are included in your HER2 IHC report? Please select all that
apply [MULTIPLE CHOICE, CLOSED-END]

A. HER2 IHC score (e.g., 0, 1+, 2+, 3+)

B. HER2 IHC result (e.g., Negative, Equivocal, Positive)

C. HER2-low IHC result (e.g., specifically callout HER2-low)

D. No inclusion of IHC result or score

7. Please select the reporting metric that you most consistently use to indicate percentage of cell
positivity. Please select one [SINGLE CHOICE, CLOSED-END]

A. Exact % of HER2-positive cells (e.g., 1%, 10%, 12%)

B. % range of HER2-positive cells (e.g., 0-5%, 10-20%)

C. % threshold of HER2-positive cells (e.g., <10%, ≥10%)

D. No reporting of % cell positivity

7
8. Please select the reporting metric that you most consistently use to indicate degree of
membrane staining, if at all. Please select one [SINGLE CHOICE, CLOSED-END]

A. Exact % of cells with membrane staining

B. % range of cells with membrane staining (e.g., 0-10%, >50%)

C. Membrane staining intensity (e.g., weak/faint vs intense)

D. Membrane staining pattern (e.g., complete vs incomplete)

E. No inclusion of membrane staining

9. Do you provide explanatory comments in the report for clinical context? Please select all that
apply [MULTIPLE CHOICE, CLOSED-END]

A. Yes, I provide comments for HER2 positive results

B. Yes, I provide comments for HER2 negative results

C. Yes, I provide comments for HER2-low results

Other [IF OTHER IS SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER TO PROCEED TO NEXT
D.
QUESTION]

E. No, I do not provide comments

10. Using your laboratory’s IHC testing method, please rate the difficulty in assigning a sample one
of the following HER2 staining categories. Please rate on a scale of 1-5 (where 1-not difficult, 3-
moderate, 5-very difficult) [SINGLE CHOICE, MUST ANSWER EACH ROW]
A. IHC score 0 o 1 o 2 o 3 o 4 o 5

B. IHC score 1 o 1 o 2 o 3 o 4 o 5

C. IHC score 2+ o 1 o 2 o 3 o 4 o 5

D. IHC score 3+ o 1 o 2 o 3 o 4 o 5

11. Please rate the difficulty in differentiating HER2 IHC 0 status, with or without membrane
staining. Please rate on a scale of 1-5 (where 1-not difficult, 3-moderate, 5-very difficult)
[SINGLE CHOICE, MUST ANSWER EACH ROW]
A. With membrane staining present o 1 o 2 o 3 o 4 o 5

8
 B. Without membrane staining present o 1 o 2 o 3 o 4 o 5

12. Please select which reporting option you believe is best suited for metastatic breast cancer
tumors which are classified as HER2 IHC 0 but have expression present (i.e., not meeting 1+
criteria but exhibiting HER2 expression). Assume a drug is approved for this novel patient
population. Please select one [SINGLE CHOICE, CLOSED-ENDED]
A. HER2 0 (>0-10%)
B. HER2 0 (membrane staining observed)
C. HER2 >0<1+
D. HER2 0 (% of cells stained with HER2)
E. HER2 >0 (membrane staining observed)

13. Please select which reporting option you would preferably use to describe and identify
metastatic breast cancer tumors which are classified as HER2 IHC 0 but have expression present
(i.e., not meeting 1+ criteria but exhibiting HER2 expression). Assume a drug is approved for
this novel patient population. Please select one [SINGLE CHOICE, CLOSED-ENDED]
A. ASCO/CAP Recommendation: HER2 0
Additional Comment: membrane staining observed

B. CDx Package Insert Recommendation: HER2 >0<1+

Section 2: Current awareness and perception of HER2-low

We would now like to investigate your current understanding and awareness of low levels of HER2
expression in breast cancer tumors.

14. How familiar are you with scoring protocols for reporting HER2-low in breast cancer? Please
rate on a scale of 1-5 (where 1-not aware, 3-somewhat familiar, 5-very familiar) [SINGLE
CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

15. Which of the following IHC scores would classify a tumor as being HER2-low? Please select one
[SINGLE CHOICE, CLOSED-END]

9
 A. IHC 0 only
B. IHC 1+ only
C. IHC 2+ only
D. IHC 2+ / ISH- only
E. IHC 2+ / ISH+ only
F. IHC 1+ or IHC 2+ / ISH-
G. IHC 1+ or IHC 2+ / ISH+
H. IHC 3+ only

16. How was your reporting template for HER2-low developed? Please select one [SINGLE CHOICE,
CLOSED-END]
I used the ASCO-CAP (American Society of Clinical Oncology and College of American
A.
Pathologists) template for reporting HER2-low results
I used the ESMO (European Society of Medical Oncology) protocols for reporting HER2-low
B.
results
I used a reporting template provided by local professional societies [WAIT] (Please specify) [IF
C. OPTION IS SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER TO PROCEED TO NEXT
QUESTION]
D. I used a reporting template unique to our laboratory / hospital or one in our area
Other [WAIT] (Please specify) [IF OTHER IS SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER
E.
TO PROCEED TO NEXT QUESTION]
F. I do not currently report out HER2-low results

17. What is your estimate for the prevalence of HER2-low amongst cases of metastatic breast
cancer? Please provide your response below [1-3 DIGIT NUMERIC]
[XXX] % of metastatic breast cancer cases

18. How would you assess the level of communication between pathologists and oncologists
around HER2-low in breast cancer today? Please rate on a scale of 1-5 (where 1-no
communication, 3-moderate, 5-high) [SINGLE CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

10
19. Since the approval of HER2-low directed treatments, which of the following, if any, are being
asked for by oncologists? Please select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. Re-testing of prior samples
B. Re-scoring of prior samples
C. Education on HER2-low status
Other [WAIT] (Please specify) [IF OTHER SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER TO
D.
PROCEED TO NEXT QUESTION]
E. None of the above

20. Since the approval of HER2-low directed treatments, which topics are discussed between
pathologists and oncologists? Please select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. Updated reporting guidelines
B. Assay selection
C. Biopsy selection
D. Recent HER2-low clinical data
E. Novel therapies
Other [WAIT] (Please specify) [IF OTHER SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER TO
F.
PROCEED TO NEXT QUESTION]
G. None of the above

21. How have you been trained on HER2-low interpretation in breast cancer? Please select all that
apply [MULTIPLE CHOICE, CLOSED-END]
A. CAP seminars
B. Professional societies
C. Industry-sponsored training
D. Self-guided training (e.g., package insert documents)
Other [WAIT] (Please specify) [IF OPTION SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER
E.
TO PROCEED TO NEXT QUESTION]
F. I have not received training

22. Through which engagement platforms have you received training on HER2-low interpretation in

11
 breast cancer? Please select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. In-person educational programs (e.g., congresses)
B. Virtual education programs (e.g., online modules)
C. Print-outs or mailed materials (e.g., pamphlets, instruction manuals)
D. Other [WAIT] (Please specify) [IF OPTION SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER TO
PROCEED TO NEXT QUESTION]
E. I have not received training

23. Of the following options, which would be your preferred source for HER2 directed learning?
[SINGLE CHOICE, CLOSED-END]
A. Industry-developed content (e.g., from pharma companies)
B. Professional organization-developed content (e.g., from national pathology societies)

Section 3: Impact of Market Events on HER2 Testing and Reporting

We would like to get your perceptions regarding recent events in HER2 testing, and how these may
impact lab practices in the future. Assume HER2-low is defined as IHC 1+ or IHC 2+/ISH-.

24. How familiar are you with the following developments related to HER2-low expression in
advanced metastatic breast cancer? Please rate on scale from 1-5 (where 1-not aware, 3-
somewhat familiar, 5-very familiar) [SINGLE CHOICE, MUST ANSWER EACH ROW]
A. ASCO-CAP guideline update
“Human Epidermal Growth
o 1 o 2 o 3 o 4 o 5
Factor Receptor 2 Testing in
Breast Cancer”
B. New England Journal of
Medicine (NEJM) publication
o 1 o 2 o 3 o 4 o 5
readout on previously treated
HER2-low breast cancer
C. European Society of Medical
Oncology (ESMO) expert
consensus on the diagnosis and o 1 o 2 o 3 o 4 o 5
management of HER2-Low
breast cancer
D. [SHOW IF FR RESPONDENT] o 1 o 2 o 3 o 4 o 5
Update to HER2 reporting in

12
 Groupe d'Etude des Facteurs
Pronostiques IHC dans le
Cancer du Sein (GEFPICS) group
guidelines
E. [SHOW IF DE RESPONDENT]
Veröffentlichung in „Die
Pathologie“ Neue
Therapiemöglichkeiten beim o 1 o 2 o 3 o 4 o 5
metastasierten HER2-low-
Mammakarzinom (Denkert et
al., 2022)

25. Please indicate which action you would take if the Ventana 4B5 assay were to be approved by
regulatory authorities as a clinically validated CDx for HER2-low. Please select one [SINGLE
CHOICE, CLOSED-END]
A. I will maintain using my current assay/antibody
B. I will switch to the validated Ventana 4B5 assay
C. I will switch to a lab-developed 4B5 assay
I would switch to another assay [WAIT] (Please specify the assay/antibody and rationale) [IF
D.
OPTION SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER TO PROCEED TO NEXT QUESTION]

26. If the treating oncologist was considering prescription of a HER2-low directed treatment for a
breast cancer patient previously reported as negative (i.e., IHC 0), how would you reconcile
your prior HER2 assessment? Please select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. I would conduct a new HER2 test using preserved tissue blocks
B. I would re-score existing slides
C. I would re-biopsy the patient and perform a new HER2 test
D. No action, I am confident with my prior scoring of HER2

27. How would you rate your preparedness for HER2-low with regards to the following topics?
Please rate on scale from 1-5 (where 1-not prepared, 3-somewhat prepared, 5-very prepared)
[SINGLE CHOICE, MUST ANSWER EACH ROW]
Staining protocol
A. validated for low levels of o 1 o 2 o 3 o 4 o 5
HER2 expression

13
 Interpreting low levels of
B. HER2 expression (HER2 o 1 o 2 o 3 o 4 o 5
IHC 1+ and 2+)
Training technical staff on
C. o 1 o 2 o 3 o 4 o 5
updated testing protocols
Communicating and
D. reporting HER2-low o 1 o 2 o 3 o 4 o 5
status to oncologists

28. How have oncologists’ interest in and focus on identifying low levels of HER2 expression shifted
within the last 6 months? [SINGLE CHOICE, CLOSED-END]
A. No oncologist has requested identification of low HER2 expression in breast cancer samples
A few oncologists have requested identification of low HER2 expression in breast cancer
B.
samples
C. Most oncologists have requested identification of low HER2 expression in breast cancer samples
D. All oncologists have requested identification of low HER2 expression in breast cancer samples

29. How have oncologists’ interest in and focus on re-testing archived samples previously scored as
IHC 0 shifted within the last 6 months? [SINGLE CHOICE, CLOSED-END]
A. No oncologist has requested re-testing of archived patient samples
B. A few oncologists have requested re-testing of archived patient samples
C. Most oncologists have requested re-testing of archived patient samples
D. All oncologists have requested re-testing of archived patient samples

30. How have oncologists’ interest in and focus on re-assessing/re-interpreting prior slides scored
as IHC 0 using new biopsies shifted within the last 6 months? [SINGLE CHOICE, CLOSED-END]
A. No oncologist has requested re-assessing of prior slides
B. A few oncologists have requested re-assessing of prior slides
C. Most oncologists have requested re-assessing of prior slides
D. All oncologists have requested re-assessing of prior slides

31. To what extent is your laboratory sufficiently prepared to accurately identify HER2-low tumors?

14
 Please rate on a scale of 1-5 (where 1-not prepared, 3-Adequately prepared, 5-optimally
prepared) [SINGLE CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

32. In your opinion, to what extent do you agree that HER2-low is a clinically validated actionable
biomarker for guiding treatment of advanced or metastatic breast cancer with HER2-targeted
agents? Please rate on a scale of 1-5 (where 1-strongly disagree, 3-neutral, 5-strongly agree)
[SINGLE CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

33. What is your level of awareness of HER2 ultra-low as a distinct biomarker classification? Please
rate on a scale of 1-5 (where 1-not aware, 3-somewhat aware, 5-highly aware) [SINGLE
CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

34. What is your estimate for the prevalence of HER2-ultra low amongst cases of metastatic breast
cancer? Please provide your response below [1-3 DIGIT NUMERIC]

[XXX] % of metastatic breast cancer cases

35. Beyond breast cancer, what is your level of awareness of HER2-low as a tumor agnostic
biomarker (i.e., in other solid tumors)? Please rate on a scale of 1-5 (where 1-not aware, 3-
somewhat aware, 5-highly aware) [SINGLE CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

36. What is your level of awareness of recent publications on HER2 migration status as an indicator
for disease metastases? Please rate on a scale of 1-5 (where 1-not aware, 3-somewhat aware,
5-highly aware) [SINGLE CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

Section 4: Use and Impact of Digital Pathology

Finally, we would like to get your perceptions regarding your current and expected future use of digital
pathology as an aid to HER2 test result interpretation.

37. Is your lab currently equipped with a slide scanner that can be used to image clinical samples

15
 for analysis using digital pathology? Please select one [SINGLE CHOICE, CLOSED-END]
Yes [WAIT] (Please specify scanner model name and reason for use) [IF OPTION IS SELECTED,
A.
PARTICIPANTS MUST SPECIFY IN ORDER TO PROCEED TO NEXT QUESTION]
B. No

38. Does your lab currently employ image analysis via digital pathology to aid in the clinical
interpretation of HER2 expression? Please select one [SINGLE CHOICE, CLOSED-END]
A. Yes
B. No

39. Are you currently using digital pathology solutions for routine diagnostics in your institution?
Please select all that apply [MULTIPLE CHOICE, CLOSED-END]

A. Yes, we use whole slide images for primary diagnosis

B. Yes, we use whole slide images for second opinions/telepathology

C. Yes, we use AI/image analysis as ancillary tools to assess predictive biomarkers

D. No, we do not currently use digital pathology tools

40. If an image analysis algorithm was to be clinically validated and approved by a regulatory
agency for assessment of HER2 expression status, in which clinical cases would you utilise this
test vs. assessing HER2 status by eye alone? Please select all that apply [MULTIPLE CHOICE,
CLOSED-END]
A. For all breast cancer cases
B. For borderline cases
C. I would not use it

41. To what degree do you think image analysis via digital pathology will play an increasingly
important role in aiding the interpretation of HER2-low expression in breast cancer? Please
rate on a scale of 1-5 (where 1-no change, 3-neutral, 5-high) [SINGLE CHOICE, CLOSED-END]
o 1 o 2 o 3 o 4 o 5

42. How would you rate the following factors as drivers of credibility for image analysis algorithms?

16
 Please rate on a scale of 1-5 (where 1-non-factor, 3-neutral, 5-strong) [SINGLE CHOICE PER
ROW, CLOSED-END]
A. FDA approved or CE-IVD marked o 1 o 2 o 3 o 4 o 5

Analytical concordance with results

B. generated by a clinically-validated o 1 o 2 o 3 o 4 o 5
reference test
Studies comparing image analysis
C. algorithm results vs. consensus o 1 o 2 o 3 o 4 o 5
opinion of a group of pathologists
Clinical validation using patient
D. samples with known treatment o 1 o 2 o 3 o 4 o 5
outcomes

43. How would you rate the following factors as driving the adoption of image analysis via digital
pathology tools? Please rate on the scale of 1-5 (where 1-non-factor, 3-neutral, 5-strong)
[SINGLE CHOICE PER ROW, CLOSED-END]

A. Shorter time to interpretation / o 5

o 1 o 2 o 3 o 4
faster turnaround time of results
B. Increased accuracy, consistency, o 5
o 1 o 2 o 3 o 4
and precision of diagnosis
C. Automated analysis o 1 o 2 o 3 o 4 o 5

D. Facilitates faster treatment starts o 1 o 2 o 3 o 4 o 5

E. Cost savings o 1 o 2 o 3 o 4 o 5

F. Time saving by decreasing staff

management of glass slides and
o 1 o 2 o 3 o 4 o 5
the opportunity to review slides
remotely
G. Laboratory and office space
saving (if sending out to
o 1 o 2 o 3 o 4 o 5
reference lab with digital
pathology tool)
H. Other [WAIT] (Please specify) [IF o 1 o 2 o 3 o 4 o 5
OTHER IS SELECTED,
PARTICIPANTS MUST SPECIFY IN
ORDER TO PROCEED TO NEXT

17
 QUESTION]

44. What are the barriers preventing the use and adoption of image analysis and digital pathology
tools? Please select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. High costs of implementation, i.e. capital expenditure on scanners and computing equipment
B. Need for lab technicians to be trained up on scanner use and maintenance
C. Technological limitations
D. Lack of need or demand
E. Integration of digital / computational pathology reports with hospital EMR system
F. Privacy concerns with storage of patient digital images
G. Storage of the large amounts of image data generated
H. Time required for workflow incorporation
I. Maintenance
J. Ongoing quality assurance (QA) programs
K. Lack of reimbursement
L. Lack of guideline inclusion
Other [WAIT] (Please specify) [IF OTHER IS SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER
M.
TO PROCEED TO NEXT QUESTION]

45. What other methodologies or technologies could be used to aid in the interpretation of HER2-
low? Select all that apply [MULTIPLE CHOICE, CLOSED-END]
A. Quantitative Continuous Scoring (QCS)

B. RNAscope™
C. mRNA expression
D. Mass spectrometry
E. Liquid biopsy
F. AI image analysis
G. Other [WAIT] (Please specify) [IF OTHER IS SELECTED, PARTICIPANTS MUST SPECIFY IN ORDER
TO PROCEED TO NEXT QUESTION]
H. I don’t know

18
Thank you for your participation in our market research.

19