An Observational Study on Human Epidermal Growth Factor Receptor (HER) 2 Status of Breast Invasive Carcinoma in Latin American Participants

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02535026
• Collaborator: (none)
• Enrollment: 580
• Locations: 4
• Duration (Months): 29
• Patients Per Site: 145
• Patients Per Site Per Month: 5

Study Details

Study Description

Brief Summary

This is a descriptive, prospective, observational and epidemiological study on participants recently diagnosed with breast cancer to evaluate the HER2 status by IHC and SISH procedures.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer

Study Design

• Study Type: Observational
• Actual Enrollment: 580 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Epidemiological, Prospective and Observational Study on the HER2 Status in Breast Invasive Carcinomas Assessed by Immunohistochemistry (IHC) and Silver In-situ Hybridization (SISH) in a Sample of Latin-American Patients
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Breast Cancer Participants Breast tissue samples from female participants with a breast cancer diagnosis that undergo an anatomopathological examination of surgical specimens and/or core needle biopsies will be considered for analysis in this study.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Status in Breast Cancer Specimens Using Immunohistochemistry (IHC) and Silver In-Situ Hybridization (SISH) Procedures [Baseline up to 30 months]

   HER2 status of the collected tissue samples was determined based on the results obtained from IHC test and SISH procedure. The IHC test gives a score of 0 to 3 positive (+) that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it's called "HER2 negative (-)." If the score is 2+, it's called "borderline." A score of 3+ is called "HER2 positive." Tissue samples which had the IHC score of 2+ (borderline) were re-tested using SISH procedure for confirmation of the HER2 status. Tissue samples with SISH test results + were considered as HER2+. Tissue samples for which HER2 status was not determined were considered as HER2 equivocal.

2. Percentage of Participants With Different Phenotypes of Breast Cancer [Baseline up to 30 months]

   Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were estrogen receptor (ER) + and/or progesterone receptor (PR) +, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Histological grading was done by Nottingham Histologic Score system based on three factors, a) the amount of gland formation (differentiation), b) the nuclear features (pleomorphism) and c) the mitotic activity. Each of these features is scored from 1-3, and then each score is added to give a final total score ranging from 3-9. The final total score is used to determine the grade in the following way: i) Grade 1 tumors have a score of 3-5, ii) Grade 2 tumors have a score of 6-7, and iii) Grade 3 tumors have a score of 8-9.

3. Percentage of Participants With Histological Sub-types of Breast Cancer [Baseline up to 30 months]

   Histological subtypes of breast cancer included ductal carcinoma, lobular carcinoma, mucinous carcinoma, mixed carcinoma, metaplastic carcinoma, and others.

4. Percentage of Participants With ER Status (Positive or Negative) Across Different Age Groups [Baseline up to 30 months]

   Participants were categorized in to following age groups: a) less than (<) 40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) greater than or equal to (≥) 70 years.

5. Percentage of Participants With ER Status (Positive or Negative) Based on Nuclear Grades [Baseline up to 30 months]

   Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.

6. Percentage of Participants With ER Status (Positive or Negative) Based on Lymphovascular Invasion [Baseline up to 30 months]

   Lymphovascular invasion is entering of breast cancer cells in to the lymph or vascular/blood channels.

7. Percentage of Participants With PR Status (Positive or Negative) Across Different Age Groups [Baseline up to 30 months]

   Participants were categorized in to following age groups: a) <40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) ≥70 years.

8. Percentage of Participants With PR Status (Positive or Negative) Based on Nuclear Grades [Baseline up to 30 months]

   Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.

9. Percentage of Participants With PR Status (Positive or Negative) Based on Lymphovascular Invasion [Baseline up to 30 months]

   Lymphovascular invasion is entering of breast cancer cells in to the lymph or vascular/blood channels.

10. Percentage of Participants With HER2 Status (Positive or Negative) Across Different Age Groups [Baseline up to 30 months]

    Participants were categorized in to following age groups: a) <40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) ≥70 years.

11. Percentage of Participants With HER2 Status (Positive or Negative) Based on Nuclear Grades [Baseline up to 30 months]

    Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.

12. Percentage of Participants With HER2 Status (Positive or Negative) Based on Lymphovascular Invasion [Baseline up to 30 months]

    Lymphovascular invasion is entering of breast cancer cells in to the lymph or blood/vascular channels.

13. Percentage of Participants With Different Phenotypes of Breast Cancer Across Different Age Groups [Baseline up to 30 months]

    Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Participants were categorized in to following age groups: a) <40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) ≥70 years.

14. Percentage of Participants With Different Phenotypes of Breast Cancer Based on Nuclear Grades [Baseline up to 30 months]

    Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.

15. Percentage of Participants With Different Phenotypes of Breast Cancer Based on Lymphovascular Invasion [Baseline up to 30 months]

    Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Lymphovascular invasion is entering of breast cancer cells in to the lymph or vascular/blood channels.

16. Percentage of Participants With Different Phenotypes of Breast Cancer Based on ER Status [Baseline up to 30 months]

    Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.

17. Percentage of Participants With Different Phenotypes of Breast Cancer Based on PR Status [Baseline up to 30 months]

    Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.

18. Percentage of Participants With Different Phenotypes of Breast Cancer Based on HER2 Status [Baseline up to 30 months]

    Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.

19. Percentage of Participants With Breast Cancer Phenotypes Among Different Hispanic Countries [Baseline up to 30 months]

    Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Anatomopathological samples (surgical specimens or when a surgical sample is not possible, a core needle biopsy may be used) from female participants with a histopathological diagnosis of invasive breast cancer

Exclusion Criteria:

• Samples whose residual material in the paraffin block(s) is insufficient for neoplasm representation in the procedures in this study

• Cancer samples that have received previous chemotherapy treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Lima		Peru	LIMA 11
2		Lima		Peru	Lima 13
3		Lima		Peru
4		Montevideo		Uruguay	11600

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02535026
• Other Study ID Numbers: ML25371
• First Posted: Aug 28, 2015
• Last Update Posted: Apr 10, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Carcinoma

Study Results

Participant Flow

Arm/Group Title	Breast Cancer (BC) Participants
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies were considered for analysis in this study.
Period Title: Overall Study
STARTED	580
COMPLETED	580
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Breast Cancer Participants
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies were considered for analysis in this study.
Overall Participants	580
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	580 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Status in Breast Cancer Specimens Using Immunohistochemistry (IHC) and Silver In-Situ Hybridization (SISH) Procedures
Description	HER2 status of the collected tissue samples was determined based on the results obtained from IHC test and SISH procedure. The IHC test gives a score of 0 to 3 positive (+) that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it's called "HER2 negative (-)." If the score is 2+, it's called "borderline." A score of 3+ is called "HER2 positive." Tissue samples which had the IHC score of 2+ (borderline) were re-tested using SISH procedure for confirmation of the HER2 status. Tissue samples with SISH test results + were considered as HER2+. Tissue samples for which HER2 status was not determined were considered as HER2 equivocal.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples from all participants who were willing to participate in the study.

Arm/Group Title	Breast Cancer Participants
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies were considered for analysis in this study.
Measure Participants	580
Measure Tissue samples	580
HER2 negative	79.1 13.6%
HER2 positive	19.8 3.4%
HER2 equivocal	1 0.2%

2. Primary Outcome

Title	Percentage of Participants With Different Phenotypes of Breast Cancer
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were estrogen receptor (ER) + and/or progesterone receptor (PR) +, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Histological grading was done by Nottingham Histologic Score system based on three factors, a) the amount of gland formation (differentiation), b) the nuclear features (pleomorphism) and c) the mitotic activity. Each of these features is scored from 1-3, and then each score is added to give a final total score ranging from 3-9. The final total score is used to determine the grade in the following way: i) Grade 1 tumors have a score of 3-5, ii) Grade 2 tumors have a score of 6-7, and iii) Grade 3 tumors have a score of 8-9.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included all breast cancer tissue samples for which the phenotype could be identified.

Arm/Group Title	Breast Cancer Participants
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies were considered for analysis in this study.
Measure Participants	574
Measure Tissue samples	574
Luminal A	31.9 5.5%
Luminal B	35 6%
HER2 Enriched	12.1 2.1%
Triple Negative	20.9 3.6%

3. Primary Outcome

Title	Percentage of Participants With Histological Sub-types of Breast Cancer
Description	Histological subtypes of breast cancer included ductal carcinoma, lobular carcinoma, mucinous carcinoma, mixed carcinoma, metaplastic carcinoma, and others.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples from all participants who were willing to participate in the study.

Arm/Group Title	Breast Cancer Participants
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies were considered for analysis in this study.
Measure Participants	580
Measure Tissue samples	580
Ductal carcinoma	78.3 13.5%
Lobular carcinoma	10.9 1.9%
Mucinous carcinoma	3.6 0.6%
Mixed carcinoma	1.2 0.2%
Metaplastic carcinoma	1.2 0.2%
Others	4.8 0.8%

4. Primary Outcome

Title	Percentage of Participants With ER Status (Positive or Negative) Across Different Age Groups
Description	Participants were categorized in to following age groups: a) less than (<) 40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) greater than or equal to (≥) 70 years.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples from all participants who were willing to participate in the study.

Arm/Group Title	Breast Cancer Participants (ER-)	Breast Cancer Participants (ER+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with ER- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with ER+ status were included in this group.
Measure Participants	203	377
Measure Tissue samples	203	377
<40 years	9.4 1.6%	6.4 NaN
40-49 years	19.7 3.4%	21.8 NaN
50-59 years	30.0 5.2%	24.4 NaN
60-69 years	22.7 3.9%	24.4 NaN
≥70 years	18.2 3.1%	23.1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	ER status association with age groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.280
	Comments
	Method	Chi-squared
	Comments

5. Primary Outcome

Title	Percentage of Participants With ER Status (Positive or Negative) Based on Nuclear Grades
Description	Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples from all participants who were willing to participate in the study.

Arm/Group Title	Breast Cancer Participants (ER-)	Breast Cancer Participants (ER+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with ER- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with ER+ status were included in this group.
Measure Participants	203	377
Measure Tissue samples	203	377
Nuclear grade 1	0 0%	4.8 NaN
Nuclear grade 2	30 5.2%	74 NaN
Nuclear grade 3	70 12.1%	21.2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	ER status association with nuclear grade.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

6. Primary Outcome

Title	Percentage of Participants With ER Status (Positive or Negative) Based on Lymphovascular Invasion
Description	Lymphovascular invasion is entering of breast cancer cells in to the lymph or vascular/blood channels.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples of all participants who were evaluable for this outcome measure.

Arm/Group Title	Breast Cancer Participants (ER-)	Breast Cancer Participants (ER+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with ER- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with ER+ status were included in this group.
Measure Participants	203	376
Measure Tissue samples	203	376
Present	69.5 12%	60.1 NaN
Absent	30.5 5.3%	39.9 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	ER status association with lymphovascular invasion.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.03
	Comments
	Method	Chi-squared
	Comments

7. Primary Outcome

Title	Percentage of Participants With PR Status (Positive or Negative) Across Different Age Groups
Description	Participants were categorized in to following age groups: a) <40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) ≥70 years.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples from all participants who were willing to participate in the study.

Arm/Group Title	Breast Cancer Participants (PR-)	Breast Cancer Participants (PR+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with PR- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with PR+ status were included in this group.
Measure Participants	290	290
Measure Tissue samples	290	290
<40 years	5.9 1%	9.0 NaN
40-49 years	15.9 2.7%	26.2 NaN
50-59 years	30.7 5.3%	22.1 NaN
60-69 years	26.6 4.6%	21.0 NaN
≥70 years	21.0 3.6%	21.7 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	PR status association with age groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.004
	Comments
	Method	Chi-squared
	Comments

8. Primary Outcome

Title	Percentage of Participants With PR Status (Positive or Negative) Based on Nuclear Grades
Description	Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples from all participants who were willing to participate in the study.

Arm/Group Title	Breast Cancer Participants (PR-)	Breast Cancer Participants (PR+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with PR- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with PR+ status were included in this group.
Measure Participants	290	290
Measure Tissue samples	290	290
Nuclear grade 1	2.1 0.4%	2.1 NaN
Nuclear grade 2	44.5 7.7%	72.8 NaN
Nuclear grade 3	53.4 9.2%	23.1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	PR status association with nuclear grade.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

9. Primary Outcome

Title	Percentage of Participants With PR Status (Positive or Negative) Based on Lymphovascular Invasion
Description	Lymphovascular invasion is entering of breast cancer cells in to the lymph or vascular/blood channels.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples of all participants who were evaluable for this outcome measure.

Arm/Group Title	Breast Cancer Participants (PR-)	Breast Cancer Participants (PR+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with PR- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with PR+ status were included in this group.
Measure Participants	290	289
Measure Tissue samples	290	289
Present	67.9 11.7%	58.8 NaN
Absent	32.1 5.5%	41.2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	PR status association with lymphovascular invasion.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.025
	Comments
	Method	ANOVA
	Comments

10. Primary Outcome

Title	Percentage of Participants With HER2 Status (Positive or Negative) Across Different Age Groups
Description	Participants were categorized in to following age groups: a) <40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) ≥70 years.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples of all participants who were evaluable for this outcome measure.

Arm/Group Title	Breast Cancer Participants (HER2-)	Breast Cancer Participants (HER2+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2+ status were included in this group.
Measure Participants	459	115
Measure Tissue samples	459	115
<40 years	6.8 1.2%	9.6 NaN
40-49 years	21.8 3.8%	18.3 NaN
50-59 years	23.7 4.1%	36.5 NaN
60-69 years	23.7 4.1%	24.3 NaN
≥70 years	24.0 4.1%	11.3 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	HER2 status association with age groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.056
	Comments
	Method	ANOVA
	Comments

11. Primary Outcome

Title	Percentage of Participants With HER2 Status (Positive or Negative) Based on Nuclear Grades
Description	Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples of all participants who were evaluable for this outcome measure.

Arm/Group Title	Breast Cancer Participants (HER2-)	Breast Cancer Participants (HER2+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2+ status were included in this group.
Measure Participants	459	115
Measure Tissue samples	459	115
Nuclear grade 1	3.9 0.7%	0 NaN
Nuclear grade 2	62.5 10.8%	41.7 NaN
Nuclear grade 3	33.6 5.8%	58.3 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments	HER2 status association with nuclear grade.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

12. Primary Outcome

Title	Percentage of Participants With HER2 Status (Positive or Negative) Based on Lymphovascular Invasion
Description	Lymphovascular invasion is entering of breast cancer cells in to the lymph or blood/vascular channels.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples of all participants who were evaluable for this outcome measure.

Arm/Group Title	Breast Cancer Participants (HER2-)	Breast Cancer Participants (HER2+)
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2- status were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2+ status were included in this group.
Measure Participants	458	115
Measure Tissue samples	458	115
Present	65.3 11.3%	57.4 NaN
Absent	34.7 6%	42.6 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.129
	Comments
	Method	Chi-squared
	Comments

13. Primary Outcome

Title	Percentage of Participants With Different Phenotypes of Breast Cancer Across Different Age Groups
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Participants were categorized in to following age groups: a) <40 years, b) 40-49 years, c) 50-59 years, d) 60-69 years, e) ≥70 years.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included all breast cancer tissue samples for which the phenotype was identified.

Arm/Group Title	BC Participants-Luminal A Phenotype	BC Participants-Luminal B Phenotype	BC Participants-HER2 Enriched Phenotype	BC Participants-Triple Negative Phenotype
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal A phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal B phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2 phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with triple negative phenotype were included in this group.
Measure Participants	183	201	70	120
Measure Tissue samples	183	201	70	120
<40 years	3.3 0.6%	10.4 NaN	10 NaN	6.7 NaN
40-49 years	21.9 3.8%	21.9 NaN	18.6 NaN	20 NaN
50-59 years	19.1 3.3%	28.9 NaN	38.6 NaN	25.8 NaN
60-69 years	25.1 4.3%	23.4 NaN	20 NaN	25 NaN
≥70 years	30.6 5.3%	15.4 NaN	12.9 NaN	22.5 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+), BC Participants-HER2 Enriched Phenotype, BC Participants-Triple Negative Phenotype
	Comments	Breast cancer phenotypes association with age groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.003
	Comments
	Method	ANOVA
	Comments

14. Primary Outcome

Title	Percentage of Participants With Different Phenotypes of Breast Cancer Based on Nuclear Grades
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Nuclear pleomorphism was observed and graded accordingly. Grade 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size; Grade 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape; Grade 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included all breast cancer tissue samples for which the phenotype was identified.

Arm/Group Title	BC Participants-Luminal A Phenotype	BC Participants-Luminal B Phenotype	BC Participants-HER2 Enriched Phenotype	BC Participants-Triple Negative Phenotype
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal A phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal B phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2 phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with triple negative phenotype were included in this group.
Measure Participants	183	201	70	120
Measure Tissue samples	183	201	70	120
Nuclear grade 1	5.5 0.9%	4.0 NaN	0 NaN	0 NaN
Nuclear grade 2	80.9 13.9%	65.2 NaN	25.7 NaN	31.7 NaN
Nuclear grade 3	13.7 2.4%	30.8 NaN	74.3 NaN	68.3 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+), BC Participants-HER2 Enriched Phenotype, BC Participants-Triple Negative Phenotype
	Comments	Breast cancer phenotypes association with nuclear grades.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

15. Primary Outcome

Title	Percentage of Participants With Different Phenotypes of Breast Cancer Based on Lymphovascular Invasion
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2. Lymphovascular invasion is entering of breast cancer cells in to the lymph or vascular/blood channels.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included breast cancer tissue samples of all participants who were evaluable for this outcome measure.

Arm/Group Title	BC Participants-Luminal A Phenotype	BC Participants-Luminal B Phenotype	BC Participants-HER2 Enriched Phenotype	BC Participants-Triple Negative Phenotype
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal A phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal B phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2 phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with triple negative phenotype were included in this group.
Measure Participants	182	201	70	120
Measure Tissue samples	182	201	70	120
Present	67 11.6%	56.7 NaN	54.3 NaN	75.8 NaN
Absent	33 5.7%	43.3 NaN	45.7 NaN	24.2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+), BC Participants-HER2 Enriched Phenotype, BC Participants-Triple Negative Phenotype
	Comments	phenotypes of breast cancer association with lymphovascular invasion.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.001
	Comments
	Method	ANOVA
	Comments

16. Primary Outcome

Title	Percentage of Participants With Different Phenotypes of Breast Cancer Based on ER Status
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included all breast cancer tissue samples for which the phenotype was identified.

Arm/Group Title	BC Participants-Luminal A Phenotype	BC Participants-Luminal B Phenotype	BC Participants-HER2 Enriched Phenotype	BC Participants-Triple Negative Phenotype
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal A phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal B phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2 phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with triple negative phenotype were included in this group.
Measure Participants	183	201	70	120
Measure Tissue samples	183	201	70	120
ER Status: Positive	97.8 16.9%	96 NaN	0 NaN	0 NaN
ER Status: Negative	2.2 0.4%	4 NaN	100 NaN	100 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+), BC Participants-HER2 Enriched Phenotype, BC Participants-Triple Negative Phenotype
	Comments	phenotypes of breast cancer association with ER status.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

17. Primary Outcome

Title	Percentage of Participants With Different Phenotypes of Breast Cancer Based on PR Status
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included all breast cancer tissue samples for which the phenotype was identified.

Arm/Group Title	BC Participants-Luminal A Phenotype	BC Participants-Luminal B Phenotype	BC Participants-HER2 Enriched Phenotype	BC Participants-Triple Negative Phenotype
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal A phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal B phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2 phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with triple negative phenotype were included in this group.
Measure Participants	183	201	70	120
Measure Tissue samples	183	201	70	120
PR Status: Positive	72.1 12.4%	76.6 NaN	0 NaN	0 NaN
PR Status: Negative	27.9 4.8%	23.4 NaN	100 NaN	100 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+), BC Participants-HER2 Enriched Phenotype, BC Participants-Triple Negative Phenotype
	Comments	Phenotypes of breast cancer association with PR status.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

18. Primary Outcome

Title	Percentage of Participants With Different Phenotypes of Breast Cancer Based on HER2 Status
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included all breast cancer tissue samples for which the phenotype was identified.

Arm/Group Title	BC Participants-Luminal A Phenotype	BC Participants-Luminal B Phenotype	BC Participants-HER2 Enriched Phenotype	BC Participants-Triple Negative Phenotype
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal A phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal B phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2 phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with triple negative phenotype were included in this group.
Measure Participants	183	201	70	120
Measure Tissue samples	183	201	70	120
HER2 Status: Positive	0 0%	22.4 NaN	100 NaN	0 NaN
HER2 Status: Negative	100 17.2%	77.6 NaN	0 NaN	100 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Breast Cancer Participants, Breast Cancer Participants (ER+), BC Participants-HER2 Enriched Phenotype, BC Participants-Triple Negative Phenotype
	Comments	phenotypes of breast cancer association with HER2 status.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

19. Primary Outcome

Title	Percentage of Participants With Breast Cancer Phenotypes Among Different Hispanic Countries
Description	Breast cancer phenotypes were classified in to a) Luminal A: tissue samples that were ER+ and/or PR+, HER2-, and either histologic grade 1 or 2; b) Luminal B: tissue samples that were ER+ and/or PR+ and HER2+ or ER+ and/or PR+ and HER2- and histologic grade 3; c) HER2 enriched: tissue samples that were ER-, PR-, and HER2+; d) Triple negative: tissue samples that were negative for ER, PR, and HER2.
Time Frame	Baseline up to 30 months

Outcome Measure Data

Analysis Population Description

Included all breast cancer tissue samples for which the phenotype was identified.

Arm/Group Title	BC Participants-Luminal A Phenotype	BC Participants-Luminal B Phenotype	BC Participants-HER2 Enriched Phenotype	BC Participants-Triple Negative Phenotype
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal A phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with luminal B phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with HER2 phenotype were included in this group.	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies with triple negative phenotype were included in this group.
Measure Participants	183	201	70	120
Measure Number of Tissue samples	183	201	70	120
Number [percentage of participants]	31.9 5.5%	35.0 NaN	12.1 NaN	20.9 NaN

Adverse Events

Adverse Event Reporting Description	Collection of adverse events data was not applicable as the present study was non-interventional and performed on breast cancer tissue samples obtained from breast cancer participants.
Arm/Group Title	Breast Cancer Participants
Arm/Group Description	Breast tissue samples from female participants with a breast cancer diagnosis that underwent an anatomopathological examination of surgical specimens and/or core needle biopsies were considered for analysis in this study.
All Cause Mortality
	Breast Cancer Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Breast Cancer Participants
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Breast Cancer Participants
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.