Racial and Survival Disparities in Inflammatory Breast Cancer (IBC) and non-IBC: A Population-Based Study Focused on Native Hawaiians and Other Pacific Islanders

doi:10.21203/rs.3.rs-3143571/v1

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Racial and Survival Disparities in Inflammatory Breast Cancer (IBC) and non-IBC: A Population-Based Study Focused on Native Hawaiians and Other Pacific Islanders

https://doi.org/10.21203/rs.3.rs-3143571/v1

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Background

Breast cancer has the highest incidence among all malignancies and is the second leading cause of cancer death among women in the United States. It is well known that race is an independent predictor of breast cancer mortality and advanced stage at diagnosis. Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer and has distinct clinical and biological features. Previous studies have shown that Blacks have a higher incidence of IBC than Whites. However, the proportion of IBC and the role of race on prognosis in Native Hawaiian and other Pacific Islander (NH/PI) populations with breast cancer are poorly understood. In this study, we aimed to examine the proportion of IBC to non-IBC in NH/PIs and to identify the clinicopathological, biological, and socioeconomic factors associated with the overall survival of NH/PIs compared to other races.

Methods

Utilizing a comprehensive cancer registry from the largest hospital in Hawaii, newly diagnosed primary invasive breast cancer patients diagnosed between 2000 and 2018 were identified. Univariate and multivariate Cox proportional hazards models were used to test the association between race and clinical outcomes. Variables with P-values <0.05 in the univariate analysis and race (variable of interest) were included in a multivariate analysis.

Results

The cohort included 3691 patients, 60 of whom had IBC. NH/PI race had the highest proportion of IBC compared to other races (3.44%) but was not found to be an independent poor prognostic factor in IBC (HR 1.17 [95%CI 0.26-5.22]). Conversely, NH/PI race was associated with worse survival outcomes in patients with non-IBC (HR 1.65 [95%CI, 1.14-2.39]) along with other factors such as lack of insurance, underinsured status, triple-negative breast cancer (TNBC) subtype, age, and advanced clinical stage.

Conclusions

The findings of this study highlight that NH/PIs had higher rates of IBC and inferior survival in non-IBC compared to other races but not in IBC. It is essential to disaggregate NH/PI race from Asians in future population-based research studies. Further research is needed to understand the factors contributing to higher rates of IBC and poor survival outcomes in NH/PIs with non-IBC as well as targeted interventions to improve breast cancer outcomes in this population to ultimately help improve survival rates and reduce health inequities in NH/PIs with breast cancer.

cancer disparities

inflammatory breast cancer

non-inflammatory breast cancer

Native Hawaiian

Pacific Islander

survival outcomes

Breast cancer has the highest incidence among all malignancies and is the second leading cause of cancer death among women in the United States.[1] According to the American Cancer Society and National Cancer Institute, in 2023, approximately 300,000 new cases and 44,000 deaths occurred in the United States due to breast cancer.[1] Health disparities have been a monumental healthcare issue in the United States. For example, given the improvement of screening strategies, the overall incidence of breast cancer has, on average, increased by 0.3% annually from 2004 to 2018, with the increase varying among different races.[2] Among Asians and Pacific Islanders, the annual increase was 1.4%, which is significantly higher compared to Whites, whose rate of increase was 0.4%[2]. This suggests that fewer Asian or Pacific Islanders had recommended screening in the past compared to Whites[2]. Additionally, it is well established that race is an independent predictor of mortality and advanced stage at diagnosis.[3, 4] These facts suggest the importance of investigating race in cancer research. Unfortunately, not many studies focus on small racial populations such as Native Hawaiians and Pacific Islanders (NH/PI), given that one of the major challenges in studying these populations is the limited number of patients in health databases. Even in the State of Hawaii, only approximately 10% of the residents are of Native Hawaiian and Pacific Islander race.[5]

In addition to race, it has been found that lower socioeconomic status (SES) is also associated with increased breast cancer mortality and higher clinical stage at diagnosis after adjusting for other potential confounders.[6–9] The interplay between clinicopathologic factors, socioeconomic factors, and race is becoming increasingly recognized.[10] However, establishing which element has a more significant influence has yet to be determined.[11] Moreover, although there are previous studies investigating this topic, unfortunately, many populational-based studies comprise primarily Black and White racial groups. As a result, little is known about the influence of racial disparities and SES, particularly on the outcomes of NH/PI patients with breast cancer. However, given the trend in the increase in breast cancer rates among Pacific Islanders,[12, 13] disaggregating NH/PI patients in epidemiological cancer-based research is paramount.[14]

It is also essential to differentiate Inflammatory Breast Cancer (IBC) from non-IBC. IBC is a rare but aggressive form of breast cancer, accounting for only 2–6% of all breast cancers but a disproportionate 7% of breast cancer deaths.[15] Additionally, the clinical features of IBC are distinct from those of non-IBC. Approximately 20–30% of patients with IBC present with metastatic disease at diagnosis compared to 6–10% of non-IBC patients.[15] Several previous studies demonstrated that the incidence of IBC is highest in Blacks,[15–17] which suggests that the incidence of IBC can vary depending on race. However, to the best of our knowledge, it has never been investigated in NH/PI patients, given the rarity of the disease and the limitations of databases, including the small number of NH/PI patients in previous studies. Understanding the epidemiologic characteristics of IBC among NH/PI patients can better provide new insights into the diagnostic and treatment strategies of breast cancer, potentially leading to higher cost-effectiveness and improved health outcomes.

We hypothesize that the proportion of IBC is higher amongst NH/PI populations compared to other races, and by association, these populations are correlated with poor survival outcomes. In this study, our primary objective was to identify and compare the proportion of IBC and non-IBC patients among distinct races (including PI and NH). The secondary objective was to identify the clinicopathological, biological, and socioeconomic factors associated with overall survival.

Study population

This retrospective chart review study was approved and informed consent was waived due to the study's retrospective nature by the Queen’s Medical Center’s Institutional Review Board (protocol number: RA-2019-027). We used Queen’s Medical Center Tumor Registry to identify patients with newly diagnosed primary invasive breast cancer who were diagnosed between January 1, 2000, and December 31, 2018. The patients diagnosed with other types of co-existing cancers were excluded. From the tumor registry and electronic medical record, we extracted age at diagnosis, race (White, Asian, Native Hawaiian or Pacific Islander, or Others based on the U.S. Office of Management and Budget (OMB) standard), primary insurance (private insurance, MEDICARE, MEDICAID, others, or no insurance), histology (ductal, lobular, mixed, or others), the proportion of IBC vs. non-IBC, clinical stage, estrogen receptor (ER) and/or progesterone receptor (PR) by immunohistochemical staining, and human epidermal growth factor receptor 2 (HER2) status. ER and PR positivity was defined based on the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline.[18] HER2 positivity was defined as a HER2/CEP17 fluorescence in situ hybridization (FISH) ratio of ≥ 2.0 and/or an immunohistochemical (IHC) staining score of 3+. Black or African American race is rare in Hawaii and thus was categorized as Others.

Statistical analysis

All the variables were summarized using standard descriptive statistics, and frequency tabulation was used to summarize the data. The chi-square and Fisher’s exact tests were used to assess the association between two categorical variables depending on expected values. The Kruskal-Wallis test was used to compare the distributions of continuous variables between different groups. Univariate and multivariate Cox proportional hazards models were used to investigate the association between each variable and overall survival (OS). OS was defined as the time from diagnosis to death. Patients who were alive at the date of the last follow-up were censored. Variables with P-values < 0.05 in the univariate analysis and race (variable of interest) were included in a multivariate analysis. All tests were two-sided. P-values < 0.05 were considered statistically significant. STATA, version 14 (STATA Corp, College Station, TX), was used for all analyses.

Patient characteristics

A total of 3691 patients were identified. Of those 3691 patients, 60 (1.5%) had IBC (Table 1). Twenty-six out of 60 patients with IBC (43.3%) were NH/PI. The overall proportion of NH/PI race was less in patients with non-IBC (730 of 3631 patients with non-IBC; 20.1%). Thirty-six of 60 patients with IBC (60%) had stage III disease. Of note, there is no stage I or II disease in IBC. The subtype was unknown for approximately 35% of patients with non-IBC because this information was recorded in a different non-EMR Pathology Department system, which could not be collected. Thirty of 60 patients with IBC (50%) and 2131 of 3631 patients with non-IBC (58.7%) had private insurance.

Table 1

Baseline Patient Characteristics
	IBC (N = 60) n (%)	Non-IBC (N = 3631) n (%)	P-value
Age (Median, range)	59 (29–72)	59 (22–96)	0.11
Race			< 0.001
White	12 (20)	712 (19.6)
Asian	20 (33.3)	2071 (57)
Native Hawaiian or Pacific Islander	26 (43.3)	730 (20.1)
Others	2 (3.3)	112 (3.1)
Unknown	0 (0)	6 (0.2)
Primary Insurance			< 0.001
Private insurance	30 (50)	2131 (58.7)
Medicare	12 (20)	1053 (29)
Medicaid	12 (20)	245 (6.7)
Others	3 (5)	168 (4.6)
No insurance	3 (5)	21 (0.6)
Unknown	0 (0)	13 (0.4)
Histology			0.3
Ductal	50 (83.3)	3183 (87.7)
Lobular	1 (1.7)	233 (6.4)
Mixed	0 (0)	45 (1.2)
Others	0 (0)	146 (4)
Unknown	9 (15)	24 (0.7)
Clinical Stage*			1.0
Stage I	N/A	2103 (57.9)
Stage II	N/A	1057 (29.1)
Stage IIII	36 (60)	224 (6.2)
Stage IV	20 (33.3)	131 (3.6)
Unknown	4 (6.7)	116 (3.2)
*Only Stages III and IV were used in the IBC analysis since there is no Stage I or II in IBC
Subtype			< 0.001
HR-positive/HER2-negative	23 (38.3)	1790 (49.3)
HER2-positive	22 (36.7)	316 (8.7)
TNBC	6 (10)	225 (6.2)
Unknown	9 (15)	1300 (35.8)
HR; hormone receptor, HER2; human epidermal growth factor receptor 2, TNBC; triple negative breast cancer

Racial difference in the proportion of patients with IBC to those with non-IBC

The proportion of those with IBC was highest in the NH/PI race, with 26 of 756 NH/PI having IBC (3.44%). The proportion of Whites with IBC was 1.66% (12 of 712 patients). Compared to the proportion of Whites, the NH/PI race had a significantly high proportion of IBC. (P = 0.003) (Table 2).

Table 2

Proportion of IBC by Race
Race	IBC (N = 60)	Non-IBC (N = 3631)	% of IBC among all BC cases
White	12	712	1.66
Asian	20	2071	0.96
Native Hawaiian or Pacific Islander	26	730	3.44
Others	2	112	1.75

Overall survival (OS) in patients with IBC

In a univariate cox proportional hazard model, no insurance (HR, 5.38 [95%CI, 1.47–19.7]; P = 0.01), MEDICAID (HR, 3.83 [95%CI, 1.58–9.28]; P < 0.01), TNBC subtype (HR, 5.43 [95%CI, 1.66–17.73]; P < 0.001), and clinical stage IV disease (HR, 10.58 [95%CI, 4.06–27.59]; P < 0.001) were associated with shorter OS, but NH/PI race (HR, 2.46 [95%CI, 0.81–7.45]; P = 0.11) was not. In a multivariate cox proportional hazard model adjusting for the variables with P-values < 0.05 in the univariate analysis and race, MEDICAID insurance (HR, 4.45 [95%CI, 1.1-18.03]; P = 0.04), TNBC subtype (HR, 4.46 [95%CI, 1.08–19.5]; P = 0.04), and clinical stage IV disease (HR, 10.1 [95%CI, 2.35–43.4]; P < 0.001) remained significant. NH/PI race remained a non-significant factor associated with shorter OS (HR, 1.17 [95%CI, 0.26–5.223]; P = 0.84) (Table 3).

Table 3

Univariate and Multivariate Analysis for OS Among Patients with IBC. (N = 60)
	Univariate		Multivariate
	HR (95% CI)	P-value	HR (95% CI)	P-value
Age	1.0 (0.97–1.03)	0.94
Race
White	Ref		Ref
Asian	2.1 (0.66–6.62)	0.21	0.6 (0.11–3.09)	0.54
Native Hawaiian or Pacific Islander	2.46 (0.81–7.45)	0.11	1.17 (0.26–5.22)	0.84
Others	1.34 (0.15–12.01)	0.8	27.85 (1.81-427.97)	0.02
Primary Insurance
Private insurance	Ref		Ref
MEDICARE	1.25 (0.47–3.33)	0.66	0.59 (0.12–2.89)	0.51
MEDICAID	3.83 (1.58–9.28)	< 0.01	4.45 (1.1-18.03)	0.04
Others	0.64 (0.08–4.98)	0.67	0.64 (0.07–5.56)	0.68
No insurance	5.38 (1.47–19.7)	0.01	4.08 (0.64–26.2)	0.14
Histology
Ductal	Ref
Lobular	1.29 (0.17–9.64)	0.81
Subtype
HR-positive/HER2-negative	Ref		Ref
HER2-positive	1.16 (0.48–2.78)	0.75	0.65 (0.22–1.9)	0.43
TNBC	5.43 (1.66–17.73)	< 0.001	4.6 (1.08–19.5)	0.04
Clinical Stage
Stage III	Ref		Ref
Stage IV	10.58 (4.06–27.59)	< 0.001	10.1 (2.35–43.4)	< .001

Overall survival (OS) in patients with non-IBC

Similarly to the findings in patients with IBC, in the univariate cox proportional hazard model, no insurance (HR, 5.13 [95%CI, 2.63–9.99]; P < 0.001), MEDICAID (HR, 3.1 [95%CI, 2.29–4.17]; P < 0.01), TNBC subtype (HR, 2.38 [95%CI, 1.78–3.19]; P < 0.01), and advanced clinical stage were associated with shorter OS. Additionally, NH/PI race (HR, 1.43 [95%CI, 1.13–1.81]; P < 0.001) and age (HR, 1.05 [95%CI, 1.04–1.06]; P < 0.01) were also associated with shorter OS (Table 4). In a multivariate cox proportional hazard model adjusting for the variables with P-values < 0.05, no insurance (HR, 3.34 [95%CI, 0.94–2.81]; P = 0.04), MEDICAID insurance (HR, 1.79 [95%CI, 1.15–2.77]; P = 0.01), TNBC subtype (HR, 1.76 [95%CI, 1.3–2.41]; P < 0.01), age (HR, 1.05 [95%CI, 1.04–1.07]; P < 0.01), advanced clinical stage (HR, 10.1 [95%CI, 2.35–43.4]; P < 0.001), and NH/PI race (HR, 1.65 [95%CI, 1.14–2.39]; P = 0.007) remained significant (Table 4).

Table 4

Univariate and multivariate analysis for OS among patients with non-IBC. (N = 3631)
	Univariate		Multivariate
	HR (95% CI)	P-value	HR (95% CI)	P-value
Age	1.05 (1.04–1.06)	< 0.01	1.05 (1.04–1.07)	< 0.01
Race
White	Ref		Ref
Asian	0.87 (0.7–1.07)	0.19	0.83 (0.6–1.14)	0.244
Native Hawaiian or Pacific islander	1.43 (1.13–1.81)	< 0.001	1.65 (1.14–2.39)	0.007
Others	1.34 (0.86–20.9)	0.86	1.34 (0.63–2.84)	0.45
Primary insurance
HMSA	Ref		Ref
MEDICARE	3.4 (2.84–4.08)	< 0.01	1.35 (0.94–1.95)	0.1
MEDICAID	3.1 (2.29–4.17)	< 0.01	1.79 (1.15–2.77)	0.01
Others	1.82 (1.3–2.55)	< 0.01	1.63 (0.94–2.81)	0.08
No insurance	5.13 (2.63–9.99)	< 0.01	3.34 (1.03–10.8)	0.04
Histology
Ductal	Ref
Lobular	1.0 (0.7–1.42)	0.98
Mixed	1.21 (0.66–2.2)	0.54
Others	1.07 (0.74–1.54)	0.72
Subtype
HR-positive/HER2-negative	Ref		Ref
HER2-positive	1.48 (1.05–2.09)	0.02	1.01 (0.7–1.46)	0.94
TNBC	2.38 (1.78–3.19)	< 0.01	1.76 (1.3–2.41)	< 0.01
Clinical Stage
Stage I	Ref		Ref
Stage II	1.95 (1.59–2.38)	< 0.01	2.08 (1.53–2.82)	< 0.01
Stage IIII	4.38 (3.36–5.72)	< 0.01	4.63 (3.14–6.83)	< 0.01
Stage IV	22.77 (17.68–29.3)	< 0.01	26.59 (18.3-38.64)	< 0.01

To our knowledge, this is the first study to investigate the association between patient, race, disease characteristics, socioeconomic status, and OS in a unique population focused on Native Hawaiian or other Pacific Islanders (NH/PI) with IBC and non-IBC separately. In accordance with our hypothesis, in our study, we found that NH/PI race had the highest proportion of IBC (3.44%) amongst other races and was statistically significant when compared to the ratio of Whites (P = 0.003). Among patients with non-IBC, weak or no insurance was associated with poor OS, which is consistent with previous studies on the influence of SES on survival outcomes.[6–8] NH/PI race also remained a significant factor associated with OS. However, among patients with IBC, only TNBC subtype and Stage IV disease were significantly associated with OS, and NH/PI was not associated with OS.

Despite NH/PI race having a significantly higher proportion of IBC than other races, NH/PI race was not found to be an independent poor prognostic factor amongst those with IBC. Although the reason for this lack of difference in survival in IBC is unclear at this time, we suspect the aggressive nature of IBC is likely one of the highly contributory factors. Small sample size might be another reason. Previous studies have consistently shown that for those with IBC, Black race is associated with poor prognosis.[7, 16, 19] However, other races have not reliably been shown to be independent poor prognostic factors in those with IBC.[19] One possible reason for this finding is that this could indicate unique disparities (e.g., biological variations) amongst Blacks with IBC that do not necessarily affect other races (including NH/PI race) regardless of the prevalence of the disease. However, given the rarity of IBC, small sample size again should also be considered when interpreting these results. In our study, MEDICAID insurance was also associated with worse survival amongst those with IBC, although no insurance was not a significant factor. This is likely due to small sample size (only three patients with IBC had no insurance) because patients without insurance coverage face similar challenges to patients with MEDICAID insurance, such as access to care and lower income levels.

Contrary to that stated above, NH/PI race was found to be associated with worse OS in those with non-IBC in our study. MEDICAID or uninsured, TNBC sub-type, and advanced clinical stage were also found to be poor prognostic factors. Although the exact reasoning why NH/PI race is an adverse prognostic factor is unclear, it is likely multifactorial, influenced by biological and socioeconomic causes. Uninsured and underinsured status are likely substantial contributory factors, although NH/PIs have also been found to have poor health outcomes despite being insured.[20] It has been well established that low socioeconomic status (SES) is associated with worse outcomes in patients with cancer.[6–8, 21] Among both men and women, five-year survival for all cancers combined is ten percentage points lower than those of higher SES.[21] Unfortunately, NH/PI populations have been associated with lower SES, with approximately 15% of NH/PIs living in poverty compared to 11% of Asians or 13% of Americans overall.[22] Low SES can result in lower quality of life (resulting in higher health risks), fragmentation of care, complications with health insurance, lower education, health literacy, and less access to care.[23] For example, Sentell et al. found that low health literacy was a significant predictor of poorer health outcomes in adults of NH/PI race.[24] Additionally, Taparra et al. found that within a total cohort of almost 600,000 women with stage 0-II breast cancer, NH/PI women had worse survival when compared with non-Hispanic White women.[25] NH/PI women had consistently longer times between surgery and radiation therapy. Thus, delays in care were suggested to be a significant contributory factor to the finding of increased mortality in this population.[25] These delays in care are suspected to primarily result from poor access to care in NH/PI populations due to financial or geographical hardships. Not only does this apply to local NH/PI patients in the United States but also to the majority of Pacific Islanders originating from Pacific Island Countries where medical care is limited. This requires these patients to travel long distances and at a significant cost to seek appropriate medical treatment, especially when specialty or hospital-based care is needed.[26] Subsequently, this leads to even further fragmentation of care, given that many patients have family and friends in their home countries, requiring frequent travel back, which can ultimately interrupt treatment plans as well.

In addition to socioeconomic causes, biological etiologies are also a consideration for the finding of non-IBC as an independent poor prognostic factor amongst NH/PIs in our study. Previous research has demonstrated higher incidence rates of both hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression in Native Hawaiians.[27–29] HR-positive breast cancers generally tend to have a better prognosis than HR-negative breast cancers.[30] However, HER2 overexpression in invasive breast cancers is associated with higher rates of disease recurrence, brain metastasis, and mortality.[31] HER2-positive breast cancers have also been found to have the second poorest prognosis amongst all breast cancer subtypes.[32] Since the advent of HER2-targeted therapies such as trastuzumab or pertuzumab, there has been a paradigm shift amongst patients with HER2-positive breast cancer resulting in decreased mortality rates, but if NH/PI patients are unable to receive these therapies due to poor access to care or other socioeconomic barriers, as discussed above, then perhaps HER2 overexpression could be a biological explanation for this finding. However, further investigation is necessary to determine the impact of receptor expression on mortality in NH/PIs with invasive breast carcinoma.

In our study, several limitations should be taken into consideration when interpreting our results. First, this was a retrospective chart review study. Although we controlled for race, insurance status, histology, and clinical stage, given the nature of the study, there are potential unknown confounding factors as well as other variables that were unable to be collected (e.g., distance to health care facilities, family support, and income), which could have affected our results. Second, although the sample size of the patients with non-IBC was favorable, we could only include sixty patients with IBC in our analysis. Unfortunately, this small sample size reduces the power of the study to identify slight differences and variations. However, as previously discussed, IBC is a rare form of breast cancer and can be challenging to observe, especially in smaller populations such as in Hawaii. Third, not all data was present for all patients included in the analysis. Notably, as mentioned above, the subtype of breast cancer was unknown for approximately 35% of patients with non-IBC due to the inability to collect the data from the non-EMR Pathology Department system. Lastly, the patient population included in our study was diagnosed with breast cancer between 2000 and 2018. The standard of care for those patients could have been different from the current standard of care, which could potentially affect survival outcomes.

In conclusion, our study demonstrated that NH/PI race had a significantly high proportion of IBC when compared to other races. NH/PI race was an adverse prognostic factor associated with worse OS in those with non-IBC but not in those with IBC. In patients with non-IBC, lack of insurance or underinsured status were also associated with shorter OS. Additional research needs to be conducted to further understand the unique determinants and disparities contributing to poor survival outcomes in NH/PI populations, particularly with non-IBC. Unfortunately, there are not many large, multi-center studies that focus on NH/PI populations, and the research that does include NH/PIs typically aggregates this population with Asians. However, as this study has demonstrated, disaggregating NH/PI race from Asians in population-based research is essential. By further identifying these factors, targeted interventions can be implemented to ultimately help improve survival rates and reduce health inequities in NH/PIs with breast cancer.

Acknowledgments

This research was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research.

Authors’ contributions

Gene T. Yoshikawa: Conceptualization, Data Curation, Investigation, Writing—Original Draft. Kyle SY. Miyazaki: Conceptualization, Data Curation, Investigation, Writing – Review & Editing. Jared D. Acoba: Conceptualization, Methodology, Investigation, Writing – Review & Editing. Takeo Fujii: Conceptualization, Methodology, Investigation, Formal Analysis, Writing – Review & Editing, Validation, Supervision.

Funding

This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (ZIA BC 012130).

Availability of data and materials:

Data cannot be shared publicly because of protected health information. The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki. This retrospective chart review study was approved by the Queen’s Medical Center’s Institutional Review Board (RA-2019-027). An informed consent was waived due to the retrospective nature of the study.

Consent for publication

Not applicable.

Competing interests:

The authors declare no competing interests.

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No competing interests reported.

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Racial and Survival Disparities in Inflammatory Breast Cancer (IBC) and non-IBC: A Population-Based Study Focused on Native Hawaiians and Other Pacific Islanders

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Abstract

Introduction

Methods

Study population

Statistical analysis

Results

Patient characteristics

Racial difference in the proportion of patients with IBC to those with non-IBC

Overall survival (OS) in patients with IBC

Overall survival (OS) in patients with non-IBC

Discussion

Declarations

References

Additional Declarations

Status:

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