https://orcid.org/0000-0002-8486-8477
Figures
Abstract
Introduction
Special histologic subtypes of breast cancer have a unique biological behavior and outcomes. The literature has demonstrated that histologic and phenotype subclassification of breast cancer varies according to race and populations. Our aim was to describe the clinicopathological characteristics and outcomes of breast cancer with special histological subtypes in a Latin/Hispanic population.
Methods
A retrospective study was conducted. We reviewed the medical records of patients newly diagnosed with special histological subtypes of breast cancer at a single tertiary reference cancer center in Peru from 2014 to 2019.
Results
A total of 479 patients were included, the median age at diagnosis was 55 years (range 26–89). The majority of patients were from a metropolitan area (59.1%). The most common histological subtype was lobular (34.9%), followed by mucinous (12.7%), papillary (12.5%), apocrine (6.9%), metaplastic (5.4%), medullary (3.8%), cribriform (3.3%), neuroendocrine (0.8%), and 9.2% mixed histology. 61.6% had a moderately differentiated grade. The most common phenotype at diagnosis was HR + HER2- (57.7%), followed by triple-negative breast cancer (TNBC)(13.2%), showing a similar pattern after neoadjuvant therapy (NAT); HR + HER- (61.7%), and TNBC (16.3%). At diagnosis most patients were stage T2 (40.3%), N0 (61.0%) and stage II (40.7%); while after NAT, stage I (64.7%) was the most common. In regard to NAT, 45.9% received chemotherapy, 31.5% hormone therapy, 15.7% trastuzumab, and 5.8% radiotherapy. The majority underwent mastectomy (71.4%). In relation to adjuvant treatment, 72.7% received chemotherapy, 74.1% hormone therapy, 9.4% trastuzumab, and 76.4% radiotherapy. Loco-regional and distant recurrence occurred in 4.2% and 12.7%, respectively. With a median follow-up of 97 months (8 years), the overall survival (OS) at 5 years was 82%, with patients with cribriform histology presenting the best rate (100%) compared to the worst observed in patients with metaplastic histology (54%).
Conclusions
The most frequent special histologic subtypes of breast cancer in Latino-Hispanic patients were lobular, mucinous, papillary, metaplastic, and apocrine carcinomas. Patients were diagnosed at more advanced stages and more frequently presented a TNBC phenotype compared to the non-Hispanic White population. Certain histological subtypes in our population presented worse OS rates.
Citation: Ziegler Rodriguez G, De La Cruz Ku G, Hickey A, Roberts S, Diaz-Mora SK, Ordonez A, et al. (2025) Special histological subtypes of breast cancer in a Hispanic Latino population. PLoS One 20(10): e0333139. https://doi.org/10.1371/journal.pone.0333139
Editor: Alexis G. Murillo Carrasco, OMICS, PERU
Received: April 21, 2025; Accepted: September 8, 2025; Published: October 3, 2025
Copyright: © 2025 Ziegler Rodriguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Breast cancer is the most common cancer diagnosis worldwide. In countries with a high human development index, 1 in 12 women will be diagnosed during their lifetime in contrast to 1 in 27 women in countries with a low human development index [1]. Stage at diagnosis and a predominant proportion of histologic subtypes and phenotypes vary significantly by region and race across the world [2]. For instance, on a global scale, a higher stage at diagnosis is observed in countries with a lower socioeconomic status, having serious implications on the overall prognosis of these patients. A meta-analysis found that the rate of metastatic breast cancer at initial diagnosis ranged from 0.0–6.0% in North America compared to 5.4–23.7% in Central and South American countries [2].
The differences in incidence and mortality by breast cancer cannot only be explained by global borders or social factors but rather crucial differences based on ethnic background have an impact on tumor microenvironment and biology [3,4]. For example, Black women present a higher incidence and mortality of triple-negative breast cancer (TNBC) compared to other races/ethnicities [4]. Regarding histology and phenotype, differences in the rates of both based on ethnicity have also been described [5]. A US-based epidemiologic study of breast cancer histology and phenotype in relation to ethnicity revealed higher rates of TNBC and HER2 + phenotypes in Black patients compared to non-Hispanic White patients (NHW), as well as a lower frequency of grade 1 and 2 histology in Asian/Pacific Islanders versus NHW patients.
Invasive ductal carcinoma is the most common breast cancer histology [6] and 25% of breast cancers are classified as special histologic subtypes [2,7]. According to the World Health Organization (WHO) special histologic subtypes are defined as invasive breast carcinomas with distinct architectural and structural patterns which differ from the common invasive carcinoma of no special type [8]. They have a distinct biological behavior in terms of prognosis, metastatic potential, treatment response, and outcomes and represent potential targets for therapy [8,9]. For example, tubular carcinoma has been associated with a favorable prognosis and is more frequently seen in White compared to Black patients [10]. In contrast, the metaplastic carcinoma subtype has a poorer prognosis in both races. Histologic subtypes also vary according to race and region. Higher proportions of dominant subtypes of lobular carcinoma and tubular adenocarcinoma are found in NHW compared to Hispanic White counterparts [5].
Although the clinical and biological heterogenicity of special histologic subtypes have been described, most of the literature published in this regard is from North American, European, or Asian cohorts, leaving a significant gap in knowledge of Hispanic Latin American populations. Regional and ethnic variation may influence the distribution of these subtypes as well as the sociodemographic characteristics, clinical behavior, phenotypes, therapeutic response, and survival outcomes. Moreover, these subtypes are usually excluded from clinical trials, thereby limiting the evidence to formulate guidelines in real-world practice. To date, data on the epidemiology, treatment, and outcomes of special histologic subtypes of breast cancer in Hispanic Latino populations are scarce. Therefore, to address this critical gap and contribute novel data on this topic, we sought to specifically describe and analyze the clinicopathological, therapeutic characteristics and outcomes of special subtypes of breast cancer in a Latin/Hispanic population.
Materials and methods
Study design and population
A retrospective cohort study was conducted. Medical records of patients diagnosed with breast cancer and treated at the “Instituto Nacional de Enfermedades Neoplasicias” (INEN), Lima, Peru, from January 1st, 2014 to December 31st, 2019 were reviewed. The patients were followed until October 2024. The INEN is a tertiary referral cancer center located in Lima, the capital of Peru. All patients treated at this institution are under the coverage of the Ministry of Health, which is the largest insurance network in Peru. Medical records were accessed for research purposes from 15-08-2023–15-12-2024. All the data were collected manually. Inclusion criteria were: patients 18 years and older with a confirmed pathological diagnosis of special or rare histological subtypes of breast cancer, which are defined as subtypes beyond invasive ductal carcinoma [11]; American Joint Committee on Cancer (AJCC) stages I to IV [12]; all specimens were reviewed by the Pathology Department of the Institute. Each diagnosis was independently reviewed and confirmed by at least two attending pathologists from the Breast Pathology Group of the institute. Final classification was achieved by consensus following the criteria outlined in the WHO Classification of Tumours of the Breast, 5th edition [8]. The histopathological results of the samples were reported in the same manner throughout the study period with no major changes. Exclusion criteria included patients lost to follow-up and incomplete medical records. All patients were treated according to the National Comprehensive Cancer Network guidelines.It should be noted that trastuzumab has been available in Peru since 2019 and pertuzumab since 2023, however no other immunotherapy regimens nor checkpoint inhibitors are available for HER2 positive patients or those with TNBC.
Variables
The type of residence was classified according to the United States Department of Agriculture guidelines [13]. Metropolitan areas were defined as regions with central counties containing urban areas of 50,000 people or more, while non-metropolitan areas refer to less accessible regions without urban centers. The special histologic subtypes included were based on the WHO classification system [8]: lobular, cribriform, apocrine, metaplastic, mucinous, neuroendocrine, medullary, papillary, micropapillary, tubular, mucoepidermoid, adenoid cystic, clear cell, and cystoadenocarcinoma. Mixed subtypes were defined as tumors containing two or more histological patterns, with at least one component being a special histologic subtype. All the histologic subtypes available during the study period were included to obtain a more accurate characterization of Hispanic Latino population.
Phenotypes were classified according to estrogen-receptor (ER), progesterone-receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. If HER2 was inconclusive, the patients underwent evaluation with fluorescence in situ hybridization (FISH) to confirm the positivity or negative of the result with a cut-off of two. The TNBC phenotype was defined as ER negative or <1%, PR negative or <1%, and HER2 negative. Genetic tests such as BRCA1/2 are not covered by the insurance, therefore these results were not available. All patients were classified according to the 8th edition of the AJCC and histologic subtype. Event-free survival (EFS) was defined as, the time from the date of surgery until locoregional or distant relapse in the patients who underwent surgery and as the time from diagnosis to disease progression, death or the end of the study, whichever occurred first, in patients who did not undergo surgery. Overall survival (OS) was defined as the time from diagnosis of the primary tumor until death or end of the study. Recurrence was confirmed with biopsy after clinical examination, ultrasound, computed tomography (CT) scan, magnetic resonance imaging, or positron emission tomography- computed tomography was performed.
Statistical analysis
No sample size was calculated. All the patients fulfilling the inclusion and exclusion criteria during the study period were included. Descriptive statistics were used to describe the sociodemographic, clinical, and therapeutic characteristics of the patients. Quantitative variables were described with mean and standard deviation, or median with interquartile range (IQR), depending on the normality of the variable. Qualitative variables were described with frequencies and percentages. Analysis of variance was used to assess the relationship between qualitative and quantitative variables, while chi-square or Fisher’s exact tests were used to assess the relationship between qualitative variables. Survival rates were calculated using Kaplan-Meier curves, and the Log-rank test was used to assess the differences in survival rates between different groups at 3 and 5 years of follow-up. Patients lost to follow-up were excluded from the analysis. Variables with a frequency less than four were not included in bivariate and survival analyses. Missing data for key variables, such as Ki-67, phenotype, and staging, are described in the tables. These cases were not included in the statistical analyses and no imputation was performed. Prognostic factors were calculated using Cox-regression analysis, risk of death or recurrence was expressed with hazard ratios, with 95% confidence intervals. To address any potential bias in our analysis, all the population fulfilling the eligibility criteria was included in our analysis, no sample was calculated. The Cox proportional hazard assumption was met by the goodness-of-fit-test. A p-value <0.05 was considered statistically significant. The Package for Social Sciences software version 28.0 was used for the analysis.
Ethics
This study was approved by the Institutional Review Board (IRB) of INEN (INEN 23–41). Consent was waived by the Ethics Committee due to the retrospective design of our study. Data was collected confidentially by the principal investigator after obtaining authorization to access the medical records by the IRB. The study was self-funded by the authors, with no financial support being received from any institution. All data was managed with strict confidentiality and only used for study purposes; it was de-identified and clinical information was codified (S1 File).
Results
Out of a total of 8,229 patients with breast cancer, 490 were diagnosed with special histologic subtypes of breast cancer, and of these 479 patients met the eligibility criteria (Fig 1). The mean age at diagnosis was 55.59 years (IQR 46–65.75 years), and the majority of the population lived at a metropolitan area (59.1%). The most common histologic subtype was invasive lobular carcinoma (34.9%), followed by mucinous (12.&%), papillary (12.5%), apocrine (6.9%), metaplastic (5.4%), medullary (3.8%), and cribriform (3.3%). Most of the tumors were intermediate grade (63.6%) with high Ki76 (72.3%). The most common phenotype was hormone receptor (HR) +/ HER2 – (57.7%), followed by TNBC (15.7%), HR + HER2+ (8.4%), and HR-HER2+ (5.0%). Most of patients were diagnosed as T2 (40.5) and T1 (25.8%), N0 (61.3%) and N1 (24.6%), M0 (96.0%); and stage II (41.4%) and stage III (31.0%) (Table 1).
Regarding neoadjuvant therapies, around half of the population received neoadjuvant chemotherapy (48.6%); 31.5%, hormonal therapy; 15.7%, trastuzumab; 5.8%, radiotherapy. Breast conserving surgery was performed in 28.6% of patients. Most of the patients received adjuvant therapies, 72.7%, chemotherapy; 76.4%, radiotherapy; 74.1%, hormonal therapy; and 9.4%, trastuzumab (Table 2). When assessing the pathologic characteristics after neoadjuvant therapies, 66.1% were classified as Stage I, followed by stage III (16.2%) and stage II (14.1%). The most common phenotype was HR + HER2- (61.7%) followed by TNBC (16.3%) (Table 3).
Subgroup analysis was performed according to subtypes. Most of the patients with metaplastic (57.7%) and medullary (61.1%) histology lived in non-metropolitan areas (p = 0.010). Among the metaplastic tumors, 92.3% were high grade and 80.8% of these were TNBC, followed by medullary tumors (83.3%, p < 0.001). A Ki67 > 20% was more frequently present in the medullary (94.4%), apocrine (90.9%), and metaplastic (84.6%) subtypes (p < 0.001). Advanced T stages (T3-4) were related to metaplastic (65.4%), apocrine (63.6%), and medullary (61.1%) subtypes (p < 0.001); while advanced N stages were related to apocrine (57.6%), mixed (55.8%), and metaplastic (46.2%) subtypes (p = 0.037). In terms of initial AJCC staging, the subtypes related to stage III were apocrine (57.6%), metaplastic (50.0%), and medullary (44.4%, p = 0.008) (Table 4 and S1 Table).
Further analysis of the therapeutic characteristics according to subtypes showed that the subtypes that more frequently underwent neoadjuvant chemotherapy were the apocrine (84.8%) and medullary (83.3%) subtypes, while neoadjuvant radiotherapy was administered in the metaplastic subtype (15.4%), neoadjuvant hormonal therapy was received by patients with papillary (46.7%) and apocrine subtypes (42.4%), and neoadjuvant treatment with trastuzumab was given to patients with an apocrine subtype (48.5%) (p < 0.05). Moreover, the patients who most frequently underwent mastectomy were those with metaplastic (100.0%) and apocrine (87.9%) histology. In terms of adjuvant therapies, adjuvant chemotherapy was related to medullary (94.4%), and apocrine subtypes (93.9%); adjuvant radiotherapy to cribriform (93.8%) and mixed subtypes (90.9%); adjuvant hormonal therapy to mucinous (98.4%) and lobular subtypes (91.0%); and adjuvant trastuzumab to patients with apocrine (33.3%) and cribriform subtypes (31.3%) (Table 5).
Subgroup analysis regarding pathologic characteristics and outcomes after neoadjuvant therapies according to the histological subtype revealed that the subtypes related to early stages were cribriform (100.0%) and mucinous (85.2%) (p < 0.001), while the subtypes with the highest rates of locoregional and distant recurrence had metaplastic (15.4%) and neuroendocrine histology (50.0%), respectively (p < 0.05). No differences were found in multiple or oligometastasis to solid organs among the histologic subtypes (S1 Table).
In terms of outcomes, locoregional and distant recurrence was present in 4.2% and 12.7% of patients, respectively. The most common distant metastasis was visceral oligometastasis (6.3%), followed by bone (4.4%), and multiple visceral metastases (2.1%) (Table 3). With a median follow-up of 97.7 months (8.2 years), the histologic subtype with the best OS at 5 years of follow-up was cribriform (100%); however, this subgroup included only 16 patients, therefore these findings should be interpreted with caution. Other subtypes demonstrated the following 5-year OS rates: papillary (90.0%), mixed (88.6%), mucinous (88.3%), lobular (78.9%), and apocrine (78.8%) (p = 0.001) (Table 6, ) and similar 5-year EFS rates, cribriform (100%), papillary (88.9%), mixed (87.6%), mucinous (86.1%), lobular (76.7%), and apocrine (75.8%) (p < 0.001) (Table 4, Fig 5). The phenotype with the highest 5-year OS and EFS rates was HR + HER2- (86.0% and 85.3%, respectively), while the TNBC phenotype had the worst survival rates (66.7% and 65.3%, respectively) (p < 0.05) (Table 6, Figs 6-9). According to stage, the OS and EFS were: stage I 89.4% and 89.9%; stage II, 88.1% and 80.0%; stage III, 72.4% and 59.2%; stage IV 47.1% and 41.2%; respectively (p < 0.001) (Table 6, Figs 10 and 11).
Discussion
The prevalence of histologic subtypes and phenotypes of breast cancer differ according to race and geographic location. We present one of the largest cohorts of Hispanic Latino patients with special histologic subtypes of breast cancer with unique characteristics and outcomes. Within this retrospective analysis of patients, lobular carcinoma was found to be the most frequent subtype with a prevalence of 35%, followed by mucinous, papillary, mixed, and apocrine variants. Most patients were diagnosed in stage II (40.7%), with 15.7% of TNBC. Despite half of the population receiving neoadjuvant treatment, surgical management consisted largely of mastectomy. While cribriform histology showed the most favorable outcomes, metaplastic carcinoma demonstrated poorer survival rates.
In regard to subtypes, we concluded that the most common subtype was lobular followed by mucinous and papillary. This in accordance with global reports [13,14] in which lobular carcinoma is indeed the most common amongst the special histological subtypes. In our sample, 5.8% of the patients had special histological subtypes, which is similar to a previous report in a Hispanic population [15], but significantly lower than other NHW and African-American (AA) populations with a prevalence of 5–15% [16]. In addition, a previous study reported that the incidence of these tumors increased with age, especially lobular breast cancer in which the frequency increases and reaches its peak at age 50 [17].
Although all the other subtypes represent less than 1% of the total breast cancer population, differences were found on comparison of NHW and Latin populations [18]. Subtypes such as mucinous (12.7% vs. 2%), papillary (12.5% vs. 1–2%), and apocrine (6.9% vs. < 4%) tumors were relatively more frequent, whereas mixed (9% vs. 25%), metaplastic (5.4% vs. < 1%), medullary (3.8% vs. 1–7%), cribriform (3.3% vs. 0.8–3.5%), and neuroendocrine (0.5% vs. 2–5%) carcinomas were less common [16,19,20]. These differences suggest that ethnicity may influence the prevalence of specific histological subtypes and could, therefore, affect tumor behavior, prognosis, and response to therapy.
The phenotype profile also varies according to region and race. While the most common immunohistochemical phenotype has been reported to be HR + HER2-, similar to our findings, the prevalence of TNBC differs among regions and populations. Previous literature showed that the prevalence of TNBC in Peru is 21.3% [21], which is within the upper range compared to other Latin populations with 12–24% [22], and is higher than that described in NHW women [5], and similar but lower than that of AA (15–30%) [23]. In our cohort, the lower frequency of TNBC and HER2 + tumors among the special histologic subtypes suggests that tumor biology and subtype composition may play an important role in the modulation of the expected regional or ethnic patterns of phenotypic expression [21,24]. Therefore this intersection of the prevalence of biology and population-specific subtype highlights the relevance of considering both histology and ethnic factors when evaluating disease prognosis and establishing treatment strategies [18,25].
Over 70% of patients had a ki67 of >20% which indicates a moderate proliferation rate. Of note, we found that elevated rates of ki67 persisted even after neoadjuvant chemotherapy. This phenomena has previously been described in lobular carcinomas, as they are less chemosensitive [26], resulting in lower rates of pathological response after chemotherapy, which is manifested by persistently high proliferation rates as well as lower rates of breast conserving surgery [27].
As reported in a prior meta-analysis, favorable outcomes of mucinous and papillary subtypes are largely due to intrinsic biology rather than response to chemotherapy. However, lobular and metaplastic tumors remain less responsive to systemic therapy and require surgical management [7,28,29]. This underscores the need to individualize the most adequate treatment for each patient according to their subtype, phenotype, and stage from a multidisciplinary point of view to optimize and offer the best treatment and obtain the best outcomes [30].
In relation to disease staging, most patients were found to have stage II followed by stage III tumors. Earlier stages were seen among this cohort compared to previous studies [21], which may be the result of the positive impact of multiple health campaigns such as the Plan Esperanza [31]. Lobular and metaplastic carcinomas often present at advanced stages due to diffuse or aggressive growth patterns, while mucinous tumors can be missed on physical examination
In terms of outcomes, 12.7% of patients presented distant recurrence as opposed to 4.7% developing locoregional relapse. Moreover, on assessing outcomes in lobular breast carcinoma, developed countries and studies based on NHW populations showed that the OS and event-free survival rates were 85% and 84%, respectively, while our results showed 79% and 79%, respectively. This finding might be explained by the higher stages at diagnosis among our patients and the higher frequency of TNBC [32,33] and limited availability of immunotherapy regimens. Nevertheless, when comparing only special subtypes to other different populations, the OS rates tended to show similar trends [7,34]. Lobular, cribriform, mucinous, and papillary carcinomas are all known to exhibit a lower rate of lymph node metastasis, and lobular carcinomas have less significant invasive and metastatic capabilities compared to ductal carcinoma, further explaining favorable outcomes [35]. Regarding mucinous and papillary tumors, the existing literature supports their low probability of relapse and in contrast to metaplastic tumors that display higher recurrence rates due to their aggressive nature [20,36]. In this respect, Zein et al. compared TNBC and metaplastic tumors and found that the latter displayed higher recurrence rates and a worse prognosis than TNBC [37]. Moreover, mucinous tumors tend to have lower recurrence rates due to reduced lymph node metastasis [38], hence ensuring a more favorable prognosis as well. Papillary tumors also present more favorable outcomes due to their lower histological grade as well as less aggressive features [7].
In terms of therapeutic characteristics, nearly 49% and 31% received neoadjuvant chemotherapy and hormonal therapy, respectively. Nowadays, neoadjuvant therapies play an important role in the management of breast cancer and differ across histological subtypes. Prior literature demonstrated that lobular carcinoma has a lower chemosensitivity compared to ductal carcinoma, as reflected in our study in which only one third of lobular tumors received neoadjuvant chemotherapy and approximately 50% received neoadjuvant endocrine therapy [28,39]. On the other hand, aggressive tumors, such as medullary, apocrine, and micropapillary carcinomas, present greater response to neoadjuvant chemotherapy and were therefore administered to more than 80% of our study population [39,40]. Favorable histologies such as tubular and mucinous, less frequently receive neoadjuvant chemotherapy but are administered higher rates of neoadjuvant endocrine therapy, which is consistent with their phenotypes and biologic behavior [41]. Patients with cribriform carcinoma underwent a mixed approach, with 62% of these patients receiving neoadjuvant chemotherapy and 37% neoadjuvant hormonal therapy. The heterogeneity among our population and across the subtypes underline treatment responsiveness and clinical decision-making tailored to each tumor behavior.
Our findings may have several potential applications in medical practice. First, targeted screening highlights the need to develop initiatives of community-level awareness and expand access to early detection services in Hispanic-Latino populations [42]. Second, they support the use of subtype-driven treatment strategies detecting the subtypes with the most favorable and poorest outcomes to guide risk-adjusted treatment planning with treatment de-escalation or more aggressive management. Third, these results can shape region-specific clinical guidelines, providing evidence tailored to this specific population. Fourth, they serve as a baseline for future multicenter studies [43]. Future research should aim to validate the subtype-specific survival patterns in larger multicentric cohorts and explore relevant biological markers and socioeconomic determinants. Moreover, future confirmatory studies based on our findings can serve as groundwork for personalized treatment planning and tailored management guidelines.
Another relevant area in which the results presented may be useful is that of developing artificial intelligence and a neural network-based diagnostic tool. The integration of clinical, pathological, and histological subtypes, and biomarker profiles could assist in the design of AI models as a tool for pathologists and oncologists to improve the diagnostic accuracy of rare and morphologically challenging special histologic subtypes. This tool could of great interest in community, private, and university hospitals [44,45]. These advances could potentially reduce the misdiagnosis and improve outcomes among Hispanic/Latino populations.
Despite the 6-year time period of this study, it has some limitations. Its retrospective design is intrinsically subjected to information bias, such as the fact that some clinical, pathological, and therapeutic characteristics collected from medical records were incomplete. Some patients were lost to follow-up and excluded from the analysis and this could have had an impact on the results. No BRCA1/2 or other molecular tests were available as these are not covered by the national insurance. Some patients could not be classified according to their immunohistochemical phenotypes as FISH was not performed to differentiate their HER2 receptor expression. However, this was a single institution study performed in a referral cancer institute which included all the population available, and no sample was used, and is therefore representative of the Peruvian population, Nonetheless, the present results should be interpreted with caution if extrapolated to other populations. The limited number of cases in certain special histologic subtypes (cribriform N = 16, neuroendocrine N = 4), restrict statistical power and require that outcomes for these groups be interpreted with caution. Furthermore, due to the relatively small number of patients within each special histological subtype group, performing an adjusted Cox proportional hazards model was not feasible. Therefore, our findings should be considered hypothesis-generating and may serve as a foundation for future research. Larger prospective multicentric studies are needed to validate our results, allow for more robust statistical analysis, and generate results that can be generalized to other countries and broader populations.
In conclusion, the frequency of special histologic subtypes of breast cancer in Hispanic Latino patients is unique. The most frequent subtype was lobular, followed by mucinous, papillary, mixed, and apocrine invasive carcinoma. More advanced stages were found compared to other developed countries, but similar or earlier compared to developing countries and previous studies from similar regions. The prevalence of TNBC was higher than the NHW population, but within the lower range of Hispanic populations. The Latin population with certain histological subtypes presented worse OS rates.
Supporting information
S1 File. Deidentified Excel dataset containing clinical and pathologic information on Hispanic/Latino patients diagnosed with special histologic breast cancer subtypes.
https://doi.org/10.1371/journal.pone.0333139.s001
(XLSX)
S1 Table. Clinicopathological and therapeutic characteristics of Latin-Hispanic patients with breast cancer at diagnosis according to special histologic subtype.
https://doi.org/10.1371/journal.pone.0333139.s002
(DOCX)
Acknowledgments
The authors thank the Universidad Científica del Sur for their support in the publication of this research/project.
References
- 1.
World Health Organization. Breast cancer fact sheets. [cited 9 Mar 2025]. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer
- 2. Benitez Fuentes JD, Morgan E, de Luna Aguilar A, Mafra A, Shah R, Giusti F. Global stage distribution of breast cancer at diagnosis: a systematic review and meta-analysis. JAMA Oncology. 2024;10(1):71–8.
- 3. Kim G, Karadal-Ferrena B, Qin J, Sharma VP, Oktay IS, Lin Y, et al. Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy. NPJ Breast Cancer. 2023;9(1):52. pmid:37311792
- 4. Kim G, Pastoriza JM, Condeelis JS, Sparano JA, Filippou PS, Karagiannis GS, et al. The contribution of race to breast tumor microenvironment composition and disease progression. Front Oncol. 2020;10:1022. pmid:32714862
- 5. Kong X, Liu Z, Cheng R, Sun L, Huang S, Fang Y, et al. Variation in breast cancer subtype incidence and distribution by race/ethnicity in the United States From 2010 to 2015. JAMA Netw Open. 2020;3(10):e2020303. pmid:33074325
- 6. Raghavendra AS, Bassett R Jr, Damodaran S, Barcenas CH, Mouabbi JA, Layman R, et al. Clinical characteristics and survival outcomes of metastatic invasive lobular and ductal carcinoma. JAMA Netw Open. 2025;8(4):e251888. pmid:40293750
- 7. Zhang H, Zhang N, Moran MS, Li Y, Liang Y, Su P, et al. Special subtypes with favorable prognosis in breast cancer: a registry-based cohort study and network meta-analysis. Cancer Treat Rev. 2020;91:102108. pmid:33075683
- 8.
Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ. WHO Classification of Tumours of the Breast. 5th ed. International Agency for Research on Cancer; 2020.
- 9. Pareja F, Bhargava R, Borges VF, Brogi E, Canas Marques R, Cardoso F, et al. Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes. NPJ Breast Cancer. 2025;11(1):6. pmid:39856067
- 10.
Limaiem F, Mlika M. Tubular breast carcinoma. Treasure Island (FL): StatPearls Publishing. 2025. https://www.ncbi.nlm.nih.gov/books/NBK542223/
- 11. Han Y, Wang J, Xu B. Clinicopathological characteristics and prognosis of breast cancer with special histological types: a surveillance, epidemiology, and end results database analysis. Breast. 2020;54:114–20. pmid:32979771
- 12.
Amin MB, Edge S, Greene F, American Joint Committee on Cancer. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
- 13. McCart Reed AE, Kalinowski L, Simpson PT, Lakhani SR. Invasive lobular carcinoma of the breast: the increasing importance of this special subtype. Breast Cancer Res. 2021;23(1):6. pmid:33413533
- 14. Corso G, Fusco N, Guerini-Rocco E, Leonardi MC, Criscitiello C, Zagami P, et al. Invasive lobular breast cancer: focus on prevention, genetics, diagnosis, and treatment. Semin Oncol. 2024;51(3–4):106–22. pmid:38897820
- 15. De-la-Cruz-Ku G, Luyo M, Morante Z, Enriquez D, Möller MG, Chambergo-Michilot D, et al. Triple-negative breast cancer in Peru: 2000 patients and 15 years of experience. PLoS One. 2020;15(8):e0237811. pmid:32833983
- 16. Weigelt B, Geyer FC, Reis-Filho JS. Histological types of breast cancer: how special are they? Mol Oncol. 2010;4(3):192–208. pmid:20452298
- 17. Batra H, Mouabbi JA, Ding Q, Sahin AA, Raso MG. Lobular carcinoma of the breast: a comprehensive review with translational insights. Cancer. 2023;15(22):5491.
- 18. Dieci MV, Orvieto E, Dominici M, Conte P, Guarneri V. Rare breast cancer subtypes: histological, molecular, and clinical peculiarities. Oncologist. 2014;19(8):805–13.
- 19. Han Y, Wang J, Xu B. Clinicopathological characteristics and prognosis of breast cancer with special histological types: a surveillance, epidemiology, and end results database analysis. Breast. 2020;54:114–20. pmid:32979771
- 20. Jenkins S, Kachur ME, Rechache K, Wells JM, Lipkowitz S. Rare breast cancer subtypes. Curr Oncol Rep. 2021;23(5):54.
- 21. Vallejos CS, Gómez HL, Cruz WR, Pinto JA, Dyer RR, Velarde R, et al. Breast cancer classification according to immunohistochemistry markers: subtypes and association with clinicopathologic variables in a peruvian hospital database. Clin Breast Cancer. 2010;10(4):294–300. pmid:20705562
- 22. Zevallos A, Bravo L, Bretel D, Paez K, Infante U, Cárdenas N, et al. The hispanic landscape of triple negative breast cancer. Crit Rev Oncol Hematol. 2020;155:103094. pmid:33027724
- 23. Siddharth S, Sharma D. Racial disparity and triple-negative breast cancer in african-american women: a multifaceted affair between obesity, biology, and socioeconomic determinants. Cancers (Basel). 2018;10(12):514. pmid:30558195
- 24. Mendivelso-González DF, Clavijo Cabezas D, Montoya L, Plazas Vargas M, López-Correa P, Colón E, et al. HER2-low prevalence among Hispanic/Latino women with breast cancer: a systematic review and meta-analysis. PLoS One. 2024;19(12):e0315287. pmid:39666634
- 25. Nascimento RGD, Otoni KM. Histological and molecular classification of breast cancer: what do we know? Mastology. 30:1–8. https://revistamastology.emnuvens.com.br/revista/article/view/945
- 26. Pramod N, Nigam A, Basree M, Mawalkar R, Mehra S, Shinde N. Comprehensive review of molecular mechanisms and clinical features of invasive lobular cancer. Oncologist. 2021;26(6):e943–53.
- 27. Majer M, Little EF, Jones S, Dong J, Bezdickova K, Hutton D. Similar decrease of proliferation employing Ki-67 after brief neoadjuvant hormonal treatment on invasive ductal carcinoma versus invasive lobular carcinoma. J Clin Oncol. 2021;39(15_suppl):e12606–e.
- 28. O’Connor DJ, Davey MG, Barkley LR, Kerin MJ. Differences in sensitivity to neoadjuvant chemotherapy among invasive lobular and ductal carcinoma of the breast and implications on surgery-A systematic review and meta-analysis. Breast. 2022;61:1–10. pmid:34864494
- 29. Collins PM, Brennan MJ, Elliott JA, Abd Elwahab S, Barry K, Sweeney K, et al. Neoadjuvant chemotherapy for luminal a breast cancer: Factors predictive of histopathologic response and oncologic outcome. Am J Surg. 2021;222(2):368–76. pmid:33334569
- 30. Barrios C, Sánchez-Vanegas G, Villarreal-Garza C, Ossa A, Lombana MA, Monterrosa-Blanco A, et al. Barriers and facilitators to provide multidisciplinary care for breast cancer patients in five Latin American countries: a descriptive-interpretative qualitative study. Lancet Reg Health Am. 2022;11:100254. pmid:36778924
- 31. Vidaurre T, Santos C, Gómez H, Sarria G, Amorin E, López M. The implementation of the Plan Esperanza and response to the imPACT Review. Lancet Oncol. 2017;18(10):e595–606.
- 32. De-la-Cruz-Ku G, Luyo M, Morante Z, Enriquez D, Möller MG, Chambergo-Michilot D, et al. Triple-negative breast cancer in Peru: 2000 patients and 15 years of experience. PLoS One. 2020;15(8):e0237811. pmid:32833983
- 33. De la Cruz Ku G, Desai A, Hickey A, Valcarcel B, Wareham C, Hernandez A, et al. Disparities in Triple negative breast cancer among hispanic population living in Latin America versus the United States. J Surg Oncol. 2025;131(7):1258–71. pmid:39803871
- 34. Lam AHK, Co MTH, Kwong A. Rare breast cancer histotypes-a retrospective study and literature review. J Clin Med. 2024;13(3):643. pmid:38337337
- 35. Wang S, Zhang Q, Mao X. Invasive papillary carcinoma of the breast. Front Oncol. 2024;14:1374091. pmid:38601769
- 36. Turashvili G, Brogi E, Morrow M, Hudis C, Dickler M, Norton L, et al. The 21-gene recurrence score in special histologic subtypes of breast cancer with favorable prognosis. Breast Cancer Res Treat. 2017;165(1):65–76. pmid:28577081
- 37. El Zein D, Hughes M, Kumar S, Peng X, Oyasiji T, Jabbour H, et al. Metaplastic carcinoma of the breast is more aggressive than triple-negative breast cancer: a study from a single institution and review of literature. Clin Breast Cancer. 2017;17(5):382–91.
- 38. Lu Q, Zhou H, Zhang J, Lee K, Chen L, Hong R. Clinicopathological characteristics and genomic profiling of pure mucinous breast cancer. The Breast. 2024;76:103760.
- 39. Seber ES, Iriagac Y, Cavdar E, Karaboyun K, Avci O, Yolcu A, et al. Efficacy of neoadjuvant chemotherapy in lobular and rare subtypes of breast cancer. J Coll Physicians Surg Pak. 2024;34(1):37–41. pmid:38185958
- 40. Yang Z-J, Xin F, Chen Z-J, Yu Y, Wang X, Cao X-C. Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer. BMC Cancer. 2024;24(1):134. pmid:38273267
- 41. Yang B, Shen M, Sun B, Zhao J, Wang M. Clinicopathological features and prognosis of mucinous breast carcinoma with a micropapillary structure. Thorac Cancer. 2024;15(36):2530–9. pmid:39520254
- 42. Serrano-Gomez SJ, Sanabria-Salas MC, Fejerman L. Breast cancer health disparities in Hispanics/Latinas. Curr Breast Cancer Rep. 2020;12(3):175–84. pmid:33584971
- 43. Serrano-Gómez SJ, Fejerman L, Zabaleta J. Breast cancer in Latinas: a focus on intrinsic subtypes distribution. Cancer Epidemiol Biomarkers Prev. 2018;27(1):3–10. pmid:29054978
- 44. Singh SK, Patnaik KS. Patho-AI: a perceptive breast cancer identification and classification using deep learning methods integrated with explainable AI. SN Comput Sci. 2025;6(6):619.
- 45. Petruolo OA, Pilewskie M, Patil S, Barrio AV, Stempel M, Wen HY, et al. Standard pathologic features can be used to identify a subset of estrogen receptor-positive, HER2 negative patients likely to benefit from neoadjuvant chemotherapy. Ann Surg Oncol. 2017;24(9):2556–62. pmid:28560596