Simple Summary
Breast cancers are classified according to their histological grade and subtype, both of which provide information about tumour characteristics and patient prognosis. Grade 1 breast cancers are well differentiated and generally have a favourable outcome. However, it is unclear whether different histological subtypes within this low-grade group are associated with different outcomes. We studied 364 patients with grade 1 invasive breast cancer diagnosed at a single institution. Most tumours were invasive breast carcinomas of no special type, while approximately one third represented pure special types or mixed subtypes. Survival was generally excellent, with overall survival rates of approximately 95% at 5 years and 85% at 10 years. Although patients with pure special tumour types showed numerically better survival than those with mixed subtypes, these differences were not statistically significant. Larger studies are needed to determine whether histological subtype provides additional prognostic information in patients with grade 1 breast cancer.
Keywords: breast cancer, histological grade 1, prognostic relevance
Abstract
Background: Histological grade is one of the strongest prognostic factors in invasive breast cancer. However, it remains unclear whether histological subtype provides additional prognostic information in well-differentiated (grade 1; G1) invasive breast carcinomas. This study investigated the distribution of histological subtypes in G1 breast cancers and evaluated their impact on overall survival. Methods: In this retrospective single-centre study, all patients diagnosed with G1 invasive breast carcinoma in a single institution between 2005 and 2014 were identified. Histopathological and clinical data were retrieved from institutional pathology and clinical databases. Tumours were classified as no special type (NST), pure special type, or mixed subtype. Overall survival was analysed using Kaplan–Meier estimates and compared with the log-rank test. Associations between histological subtype and mortality were evaluated using the chi-squared test. Results: Of 429 initially identified patients, 364 fulfilled the inclusion criteria. NST represented the predominant subtype (67.3%), whereas pure special types and mixed subtypes accounted for 15.1% and 15.7% of cases, respectively. Tubular carcinoma was the most frequent pure special subtype, followed by mucinous, cribriform, papillary, lobular and adenoid cystic carcinoma. After exclusion of patients with simultaneous higher-grade contralateral carcinomas, 348 patients were included in survival analyses. The overall 5- and 10-year survival rates were 94.7% and 85.4%, respectively. Pure special types showed the highest survival rates numerically, whereas mixed subtypes had the lowest. However, overall survival did not differ significantly between NST, pure special types and mixed subtypes (log-rank p = 0.39). Likewise, no significant survival differences were observed among individual pure special subtypes (p = 0.20), and no significant association between histological subtype and mortality was identified (χ2 p = 0.064). Conclusions: Within this cohort of G1 invasive breast carcinomas, no statistically significant association between histological subtype and overall survival was identified. However, clinically relevant differences cannot be excluded given the heterogeneity of the cohort and the small number of events. Larger studies incorporating multivariable analyses and breast cancer-specific outcomes are needed to further clarify the prognostic relevance of histological subtype in G1 invasive breast cancer.
1. Introduction
Breast cancer is the most common non-cutaneous malignancy in women worldwide and comprises a biologically heterogeneous group of tumours with distinct morphological, molecular and clinical characteristics [1]. Patient prognosis is determined by a combination of clinicopathological parameters, including tumour stage, lymph node status, biomarker profile, histological grade and histological subtype [1,2,3,4,5]. Among these, histological grade according to the Nottingham Grading System remains one of the most robust and reproducible prognostic factors and is routinely incorporated into therapeutic decision-making [2,4,5,6,7,8].
Approximately 75% of invasive breast carcinomas are classified as invasive carcinoma of no special type (NST), whereas the remaining tumours comprise a heterogeneous group of histological special types as defined by the World Health Organization (WHO) [2,6,9]. According to the recently updated WHO Classification of Breast Tumours (6th edition), histological subtype remains an integral component of breast cancer classification [2]. However, its independent prognostic value remains uncertain once established prognostic variables are taken into account [1,2,10,11]. Several of these special types, including tubular, mucinous and cribriform carcinoma, are generally associated with an excellent clinical outcome, whereas others, such as high grade metaplastic carcinoma, show a more aggressive biological behaviour [1,2,6,9,10,11,12,13,14,15]. However, interpretation of these observations is complicated by the fact that histological subtype is closely associated with other favourable prognostic variables, including lower histological grade, smaller tumour size and lower nodal stage [2,4,5,7,16,17,18,19].
Previous studies investigating the prognostic value of histological subtype have produced conflicting results [11,14,17,20]. While several large cohort studies demonstrated differences in outcome between individual special types, others concluded that histological subtype alone provides only limited prognostic information once established prognostic variables are considered [11,14,17,20]. In particular, histological grade appears to outweigh subtype as an independent predictor of survival [14,18,20]. Consequently, it remains uncertain whether the favourable prognosis reported for many special histological types reflects their intrinsic biology or simply their frequent association with low-grade disease [21,22,23]. In our previous study, we investigated the prognostic relevance of pure and mixed special histological subtypes in a cohort that included carcinomas of different grades [14]. In this study, we focused specifically on the potential prognostic power within the G1 group.
To address this question, studies investigating homogeneous patient cohorts are required. Restricting analyses to grade 1 carcinomas minimises one of the strongest confounding prognostic variables and allows a more direct assessment of the potential prognostic contribution of histological subtype. Despite the clinical relevance of this question, data focusing exclusively on well-differentiated invasive breast carcinomas remain scarce.
The aim of the present study was therefore (1) to determine the distribution of histological subtypes in grade 1 invasive breast carcinomas diagnosed at a large tertiary referral centre and (2) to evaluate whether histological subtype is associated with overall survival in this prognostically favourable subgroup.
2. Materials and Methods
2.1. Study Design and Patient Cohort
This retrospective single-centre cohort study included consecutive adult patients diagnosed with grade 1 (G1) invasive breast carcinoma at the Department of Pathology and Molecular Pathology, University Hospital Zurich, between 1 January 2005 and 31 December 2014. Cases were identified from the pathology database of the Pathology Institution (PathoPro, version 9.1.0.8678) using the search terms breast and G1.
Clinical and pathological data were retrieved from the pathology database and complemented by review of the electronic medical records (KISIM, version 5.6.0.14). Collected variables included patient demographics, biopsy and surgical pathology reports, histological subtype, Nottingham grade, tumour stage, lymph node status, receptor status (ER, PR and HER2), lymphovascular invasion, surgical treatment, adjuvant therapy, clinical events and follow-up. The most recent documented patient contact was used for survival analyses. The study formed part of a larger breast cancer project approved by the Ethics Committee of the Canton of Zurich (KEK-2012-553; PB-2019-00111, BASEC 2024-01804).
2.2. Histopathological Assessment
Only patients with a final diagnosis of grade 1 invasive breast carcinoma in the surgical specimen were included. Cases upgraded to grade 2 or grade 3 following surgical resection were excluded. Cases downgraded from grade 1 invasive carcinoma on core biopsy to ductal carcinoma in situ (DCIS) at excision remained eligible, and the biopsy subtype was retained for descriptive analyses.
Tumours were classified according to the current WHO criteria (4th, 5th and 6th editions of the WHO classification of breast tumours) as invasive carcinoma of no special type (NST), pure special histological type, or mixed subtype. Mixed carcinomas were defined as tumours containing more than one histological subtype, irrespective of the relative proportions of the individual components.
2.3. Statistical Analysis
Descriptive statistics were used to summarise clinicopathological characteristics and the distribution of histological subtypes. Patients with simultaneous contralateral invasive carcinomas of higher histological grade were excluded from survival analyses because prognosis is determined by the highest-grade tumour.
Overall survival was calculated from the date of diagnosis to death or last follow-up using the Kaplan–Meier method. Patients alive at the last documented follow-up were censored. Owing to the limited number of events, median survival was not reached; therefore, 5- and 10-year overall survival rates were reported. Survival distributions were compared using the log-rank test. However, overall survival was not specifically related to breast cancer-specific death.
The distribution of follow-up duration among histological groups was assessed using the Kruskal–Wallis test after confirmation of non-normality with the Kolmogorov–Smirnov and Shapiro–Wilk tests. Associations between histological subtype and mortality were analysed using the chi-squared test. Statistical analyses were performed with IBM SPSS Statistics version 30.0. A two-sided p-value < 0.05 was considered statistically significant.
3. Results
3.1. Patient Characteristics
A total of 429 patients with grade 1 breast carcinoma were initially identified. Following exclusion of 65 tumours that were upgraded to grade 2 or grade 3 in the surgical specimen, 364 patients were included in the final study cohort (Figure 1). The median age at diagnosis was 62 years (range, 33–92 years), and all patients were female (Figure 2).
Figure 1.
Chart-flow of case selection (exclusion and inclusion of patients). BC: breast cancer.
Figure 2.
Overall frequency of histological subtypes of G1 carcinomas in the whole cohort. OP: Operation.
Histological grade differed between core biopsy and surgical resection in 85 cases (19.8%). Upgrading from grade 1 at biopsy to grade 2 or grade 3 at surgical excision occurred in 65 patients (15.2%), whereas 18 tumours initially diagnosed as grade 2 on biopsy were downgraded to grade 1. In 90 patients (24.7%), no core biopsy was available for review.
Details are shown in Table 1 and Table 2. The number of surgeries per year is shown in Supplementary Table S1.
Table 1.
Patients with G1 histological grading in biopsy (n = 429).
| n (%) | |
| Patients’ characteristics | |
| Sex | |
| Female | 429 (100) |
| Male | 0 (0) |
| Age at diagnosis (years) | |
| median (IQR; range) | 61 (51–71; 33 to 92) |
| ≤50 | 91 (21.2) |
| >50 | 338 (78.8) |
| Pathological features | |
| Grading in biopsy | |
| G1 | 211 (46.2) |
| G2 | 18 (4.2) |
| No grading possible/no biopsy performed | 200 (46.6) |
| Grading changes (biopsy → surgical specimen) | |
| Any changes in grading | 85 (19.8) |
| Upgrade G1 → G2 | 59 (13.8) 59/85 (69.4) |
| Upgrade G2 → G3 | 6 (1.4) 6/85 (7.1) |
| Downgrade G2 → G1 | 18 (4.2) 18/85 (21.2) |
| Downgrade G1 → Non-invasive | 2 (0.5) 2/85 (2.4) |
| Subtypes in biopsy | 364 (84.8) |
| NST | 187/364 (51.4) |
| Pure special type | 23/364 (6.3) |
| Cribriform | 8/364 (2.2) 8/23 (34.8) |
| Lobular | 3/364 (0.8) 3/23 (13) |
| Mucinous | 3/364 (0.8) 3/23 (13) |
| Papillary | 3/364 (0.8) 3/23 (13) |
| Tubular | 6/364 (1.7) 6/23 (26.1) |
| Mixed subtype (>1 subtype) | 23/364 (6.3) |
| Non-invasive histology | 41/364 (11.3) |
| No biopsy performed/available | 90/364 (24.7) |
Table 2.
Patients with G1 carcinoma in surgical specimens (n = 364).
| n (%) | |
| Patients’ characteristics | |
| Sex | |
| Female | 364 (100) |
| Male | 0 (0) |
| Age at diagnosis (years) | |
| median (IQR; range) | 62 (52–71; 33 to 92) |
| ≤50 | 75 (20.6) |
| >50 | 289 (79.4) |
| Pathological features | |
| Grading in surgical specimen | |
| G1 | 364 (100) |
| Subtypes in surgical specimen | |
| NST | 245 (67.3) |
| Pure special type | 55 (15.1) |
| Cribriform | 11 (3) 11/55 (20) |
| Lobular | 4 (1.1) 4/55 (7.3) |
| Mucinous | 13 (3.6) 13/55 (23.6) |
| Papillary | 6 (1.6) 6/55 (10.9) |
| Tubular | 20 (5.5) 20/55 (36.4) |
| Adenoid cystic | 1 (0.3) 1/55 (1.8) |
| Mixed subtype (>1 subtype) | 57 (15.7) |
| Non-invasive histology (DCIS) | 7 (2) |
| Nodal stage | |
| pN0 | 244 (67) |
| pN1 | 40 (11) |
| pN1mi (sn) | 46 (12.6) |
| pN2 | 10 (2.8) |
| pN3 | 3 (0.8) |
| pNX or not available | 21 (5.8) |
| Tumour stage | |
| pT1 | 294 (80.8) |
| pT2 | 62 (17) |
| pT3 | 1 (0.3) |
| pT4 | 1 (0.3) |
| rpT1 | 2 (0.6) |
| rpT2 | 1 (0.3) |
| rpT4b | 1 (0.3) |
| pTX or not available | 2 (0.6) |
| M stage | |
| M0 | 348 (95.6) |
| M1 | 1 (0.3) |
| MX | 15 (4.1) |
| ER status | |
| ER strongly positive (>10%) | 350 (96.2) |
| ER low positive (1–9%) | 3 (0.8) |
| ER negative (0%) | 1 (0.3) |
| Not available | 10 (2.8) |
| PR status | |
| PR strongly positive (>10%) | 315 (86.5) |
| PR low positive (1–9%) | 17 (4.7) |
| PR negative (0%) | 19 (5.2) |
| Not available | 13 (3.6) |
| Her2 status | |
| HER positive (FISH+ and/or IHC 3+) | 1 (0.3) |
| HER negative (FISH- and/or IHC 0/1+/2+) | 352 (96.7) |
| Not available | 11 (3) |
| Events | |
| Patients with events | 31 (8.5) |
| Ipsilateral recurrence (same breast/axilla) | 10 (2.8) 10/31 (32.3) |
| Second cancer/contralateral recurrence | 15 (4.1) 15/31 (48.4) |
| Distant metastasis | 6 (1.7) 6 (1.7) |
3.2. Distribution of Histological Subtypes
Among the 364 surgical specimens, invasive carcinoma of no special type (NST) represented the predominant histological subtype (245/364, 67.3%). Pure special histological types and mixed carcinomas each accounted for 57 cases (15.7%) (Figure 2 and Figure S1).
Mixed carcinomas comprised 16 different histological combinations, most commonly NST with cribriform differentiation, NST with tubular differentiation, and NST with combined cribriform and tubular differentiation, together accounting for more than 60% of all mixed tumours (Table 3).
Table 3.
Mixed subtypes diagnosed in surgical specimens.
| n (%) | |
| Mixed subtypes in surgical specimens | |
| NST + cribriform | 18 (31.6) |
| NST + tubular | 9 (15.8) |
| NST + papillary | 1 (1.8) |
| NST + mucinous | 3 (5.3) |
| NST + lobular | 4 (7) |
| NST + micropapillary | 2 (3.5) |
| Tubular + lobular | 1 (1.8) |
| Tubular + cribriform | 1 (1.8) |
| NST + cribriform + tubular | 9 (15.8) |
| NST + cribriform + lobular | 1 (1.8) |
| NST + cribriform + papillary | 2 (3.5) |
| NST + cribriform + encapsulated non-invasive papillary carcinoma | 1 (1.8) |
| NST + tubular + lobular | 2 (3.5) |
| Tubular + lobular + papillary | 1 (1.8) |
| Tubular + lobular + cribriform | 1 (1.8) |
| NST + cribriform + lobular + tubular | 1 (1.8) |
| Total | 57 (100) |
3.3. Survival Analysis
After exclusion of 16 patients with synchronous contralateral higher-grade carcinomas, 348 patients were included in the survival analyses.
Overall survival for the entire cohort was excellent, with 5- and 10-year survival rates of 94.7% and 85.4%, respectively. During follow-up, 46 patients (13.2%) died, whereas 302 (86.8%) were censored (Supplementary Table S2).
When stratified by histological category, pure special types demonstrated the highest survival rates (5-year: 100%; 10-year: 95.7%), whereas mixed carcinomas showed numerically lower survival (5-year: 92.1%; 10-year: 79.5%). Patients with NST had survival rates comparable to those of the overall cohort. However, Kaplan–Meier analysis demonstrated no statistically significant difference in overall survival among NST, pure special types and mixed carcinomas (log-rank p = 0.39) (Figure 3).
Figure 3.
Kaplan–Meier survival curves in subtypes of G1 carcinomas (NST vs. pure special type vs. mixed subtypes) in surgical specimens in a follow-up period of 20 years. OP: Operation. There is no significant difference in overall survival stratified by histological subtype (p = 0.39).
Within the pure special-type group, only three deaths occurred during follow-up, affecting patients with cribriform, mucinous and adenoid cystic carcinoma. No deaths were observed in patients with tubular, papillary or lobular carcinoma. Survival differences between individual special histological subtypes were not statistically significant (log-rank p = 0.2) (Supplementary Figure S2).
Because mixed carcinomas comprised 16 distinct subtype combinations, many represented only one to three cases, precluding meaningful statistical comparison between individual combinations. The available dataset in this cohort does not contain the cause-of-death and longitudinal event data required for reliable analyses of these endpoints. The 46 deaths therefore represent deaths from all causes and cannot be attributed solely to breast cancer.
3.4. Follow-Up and Mortality Analyses
Follow-up duration did not differ significantly between the three principal histological groups (Kruskal–Wallis p = 0.412), confirming comparable observation periods.
Similarly, no significant association was observed between histological subtype and mortality (χ2 = 5.50, p = 0.064; Cramer’s V = 0.126), indicating only a weak relationship between histological subtype and overall survival.
4. Discussion
The present study investigated whether histological subtype provides independent prognostic information in a homogeneous cohort of patients with well-differentiated (grade 1) invasive breast carcinoma. Although numerical differences in survival were observed between histological groups, histological subtype could not be significantly associated with overall survival. These findings suggest that, within grade 1 invasive breast carcinomas, the favourable prognosis is predominantly determined by low histological grade rather than by histological subtype. However, the small number of deaths, particularly among patients with special histological subtypes, limited statistical power. No statistically significant association between histological subtype and overall survival was identified in this cohort, while clinically relevant differences cannot be excluded.
An additional noteworthy observation was the relatively high frequency of grading discordance between core biopsy and surgical excision, occurring in approximately one-fifth of cases.
Previous studies have consistently demonstrated prognostic differences between individual histological subtypes of breast carcinoma [14,18,19,20]. Tubular, mucinous and cribriform carcinomas are generally associated with excellent outcomes, whereas high grade metaplastic carcinoma and several other rare subtypes exhibit more aggressive biological behaviour [2,5,10,12,13,18,24,25]. However, most published series included tumours of all histological grades and stages. Consequently, the reported prognostic differences may, at least in part, reflect the unequal distribution of established prognostic variables rather than the independent effect of histological subtype itself [2,5,10,12,13,18,24,25].
By restricting our analysis to grade 1 carcinomas, one of the strongest prognostic determinants was largely controlled. Within this biologically favourable subgroup, histological subtype no longer demonstrated a statistically significant influence on survival. This observation is consistent with previous studies suggesting that histological grade carries greater prognostic weight than histological subtype and that subtype should be interpreted in conjunction with other clinicopathological parameters rather than in isolation [2,5,10,11,12,13,18,24,25,26].
Interestingly, patients with pure special histological types showed numerically better survival than those with NST or mixed carcinomas. Although this trend did not reach statistical significance, it is biologically plausible and in keeping with the recognised favourable behaviour of several special histological subtypes [2,5,10,11,12,13,18,24,25,26]. The absence of statistical significance is likely attributable to the relatively small number of events and the limited sample size within individual subtype categories, particularly among the rare tumour entities.
An additional finding of this study was the relatively high frequency of grading discrepancies between core needle biopsy and the corresponding surgical specimen. Approximately one-fifth of cases demonstrated a change in Nottingham grade, with most representing upgrading at surgical excision. Although not the primary objective of the present study, this observation underlines the well-recognised limitations of tumour grading on core biopsy and may warrant further investigation in larger contemporary cohorts.
Strengths and Limitations of the Study
The strengths of this study include the uniform pathological assessment at a single tertiary referral centre, the homogeneous study population restricted to grade 1 invasive breast carcinomas and the long duration of clinical follow-up, approaching 20 years in some patients. These factors reduce diagnostic variability and allow robust assessment of long-term outcome.
An important further strength of the present study is the separate analysis of mixed histological carcinomas. In routine practice, these tumours are frequently grouped according to their predominant component and are therefore underrepresented in outcome studies. Their separate evaluation provides additional insight into this clinically relevant but insufficiently studied subgroup.
Several limitations should also be acknowledged. The retrospective design inevitably introduces selection bias, while treatment modalities evolved during the study period and were not incorporated into the survival analyses. Furthermore, the relatively small number of deaths limited statistical power, particularly for analyses of individual special histological subtypes and mixed carcinomas. Consequently, small prognostic differences cannot be completely excluded.
Although treatment modalities were not incorporated into the survival analyses and evolved during the study period, all patients were managed within a single tertiary breast centre using multidisciplinary treatment recommendations, thereby reducing interinstitutional variability.
5. Conclusions
In conclusion, this study demonstrates that histological subtype alone could not be associated with significant prognostic power in grade 1 invasive breast carcinoma. These findings reinforce the central prognostic role of histological grade while supporting the continued diagnostic importance of histological subtype for tumour classification and multidisciplinary patient management. Larger multicentre studies incorporating contemporary treatment strategies are warranted to validate these observations.
Our findings do not diminish the diagnostic importance of histological subtype. Histological classification remains essential for accurate tumour diagnosis, recognition of rare entities, correlation with characteristic molecular alterations and appropriate multidisciplinary management. Rather, our results suggest that, within the specific subgroup of well-differentiated invasive breast carcinomas, histological subtype contributes only limited additional prognostic information beyond histological grade. The retrospective design introduces potential selection bias. Treatment approaches also changed during the study period and were not accounted for in the survival analyses. In addition, the small number of deaths limited statistical power, particularly for analyses of individual special histological subtypes and mixed carcinomas. Small prognostic differences therefore cannot be excluded.
Supplementary Materials
The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/cancers18193154/s1: Figure S1: Distribution of subtypes of G1 carcinomas (NST vs. pure special type vs. mixed subtypes) in surgical specimens between 2005–2014; Figure S2: Kaplan–Meier survival curves in pure special subtypes of G1 carcinomas in surgical specimens in a follow-up period of 20 years. OP: Operation. There is no significant difference in overall survival stratified to special histological subtype (p = 0.2); Table S1: Operations per year; Table S2: Survival data in 348 of 364 patients (only 348 patients were included in the survival analysis).
Author Contributions
Conceptualization, Z.V.; Methodology, E.L.; Validation, L.B. and Z.V.; Formal analysis, E.L.; Investigation, E.L. and Z.V.; Data curation, E.L. and L.B.; Writing—original draft, E.L., L.B. and Z.V.; Writing—review and editing, E.L., L.B. and Z.V.; Visualisation, L.B.; Supervision, Z.V.; Project administration, Z.V. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Cantonal Ethics Committee (KEK-2012-553 approval date: 8 May 2013; PB-2019-00111 approval date: 21 August 2019, BASEC 2024-01804 approval date: 10 June 2025) for studies involving humans.
Informed Consent Statement
Written consent for the further use of health-related data and/or biological material was obtained where available. For patients without documented consent, the further use of their data and/or biological material for this retrospective study was authorised by the responsible ethics committee (KEK-2012-553; PB-2019-00111, BASEC 2024-01804).
Data Availability Statement
The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.
Conflicts of Interest
The authors declare no conflicts of interest.
Funding Statement
This research received no external funding.
Footnotes
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
References
- 1.Watkins E.J. Overview of breast cancer. JAAPA. 2019;32:13–17. doi: 10.1097/01.JAA.0000580524.95733.3d. [DOI] [PubMed] [Google Scholar]
- 2.WHO Classification of Tumours Editorial Board . WHO Classification of Breast Tumours. 6th ed. International Agency for Research on Cancer (IARC); Lyon, France: 2026. [Google Scholar]
- 3.Rakha E.A., Reis-Filho J.S., Baehner F., Dabbs D.J., Decker T., Eusebi V., Fox S.B., Ichihara S., Jacquemier J., Lakhani S.R., et al. Breast cancer prognostic classification in the molecular era: The role of histological grade. Breast Cancer Res. 2010;12:207. doi: 10.1186/bcr2607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Elston C.W., Ellis I.O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology. 1991;19:403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
- 5.Ellis I.O., Galea M., Broughton N., Locker A., Blamey R.W., Elston C.W. Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology. 1992;20:479–489. doi: 10.1111/j.1365-2559.1992.tb01032.x. [DOI] [PubMed] [Google Scholar]
- 6.WHO Classification of Tumours Editorial Board . WHO Classification of Tumours of the Breast. 5th ed. International Agency for Research on Cancer (IARC); Lyon, France: 2019. [Google Scholar]
- 7.Rakha E.A., El-Sayed M.E., Menon S., Green A.R., Lee A.H., Ellis I.O. Histologic grading is an independent prognostic factor in invasive lobular carcinoma of the breast. Breast Cancer Res. Treat. 2008;111:121–127. doi: 10.1007/s10549-007-9768-4. [DOI] [PubMed] [Google Scholar]
- 8.Rakha E.A., El-Sayed M.E., Lee A.H., Elston C.W., Grainge M.J., Hodi Z., Blamey R.W., Ellis I.O. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J. Clin. Oncol. 2008;26:3153–3158. doi: 10.1200/JCO.2007.15.5986. [DOI] [PubMed] [Google Scholar]
- 9.WHO Classification of Tumours Editorial Board . WHO Classification of Tumours of the Breast. 4th ed. International Agency for Research on Cancer (IARC); Lyon, France: 2012. [Google Scholar]
- 10.Yerushalmi R., Hayes M.M., Gelmon K.A. Breast carcinoma—Rare types: Review of the literature. Ann. Oncol. 2009;20:1763–1770. doi: 10.1093/annonc/mdp245. [DOI] [PubMed] [Google Scholar]
- 11.Song B., Singh H. Rare Breast Cancers Review. Healthcare. 2024;12:2483. doi: 10.3390/healthcare12232483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Tseng H.S., Lin C., Chan S.E., Chien S.Y., Kuo S.J., Chen S.T., Chang T.W., Chen D.R. Pure mucinous carcinoma of the breast: Clinicopathologic characteristics and long-term outcome among Taiwanese women. World J. Surg. Oncol. 2013;11:139. doi: 10.1186/1477-7819-11-139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Sun J.Y., Zhou J., Zhang W.W., Li F.Y., He Z.Y., Wu S.G. Tubular carcinomas of the breast: An epidemiologic study. Future Oncol. 2018;14:3037–3047. doi: 10.2217/fon-2018-0385. [DOI] [PubMed] [Google Scholar]
- 14.Rechsteiner A., Dietrich D., Varga Z. Prognostic relevance of mixed histological subtypes in invasive breast carcinoma: A retrospective analysis. J. Cancer Res. Clin. Oncol. 2023;149:4967–4978. doi: 10.1007/s00432-022-04443-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Rakha E.A., Lee A.H., Evans A.J., Menon S., Assad N.Y., Hodi Z., Macmillan D., Blamey R.W., Ellis I.O. Tubular carcinoma of the breast: Further evidence to support its excellent prognosis. J. Clin. Oncol. 2010;28:99–104. doi: 10.1200/JCO.2009.23.5051. [DOI] [PubMed] [Google Scholar]
- 16.Pereira H., Pinder S.E., Sibbering D.M., Galea M.H., Elston C.W., Blamey R.W., Robertson J.F., Ellis I.O. Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology. 1995;27:219–226. doi: 10.1111/j.1365-2559.1995.tb00213.x. [DOI] [PubMed] [Google Scholar]
- 17.Makki J. Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance. Clin. Med. Insights Pathol. 2015;8:23–31. doi: 10.4137/CPath.S31563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Li C.I., Moe R.E., Daling J.R. Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years. Arch. Intern. Med. 2003;163:2149–2153. doi: 10.1001/archinte.163.18.2149. [DOI] [PubMed] [Google Scholar]
- 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;54:114–120. doi: 10.1016/j.breast.2020.09.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Li C.I., Uribe D.J., Daling J.R. Clinical characteristics of different histologic types of breast cancer. Br. J. Cancer. 2005;93:1046–1052. doi: 10.1038/sj.bjc.6602787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Anjum S., Mooghal M., Kayani N., Sattar A., Vohra L., Zeeshan S., Idress R. Mucinous Micropapillary Carcinoma of Breast in a Developing World Setting: Case Series with Clinicopathological Insights and Survival Analysis from a Tertiary Care Hospital. Case Rep. Pathol. 2026;2026:5573148. doi: 10.1155/crip/5573148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Qiu P., Cui Q., Huang S., Zhang Y., Zhang H., Luo H. An overview of invasive micropapillary carcinoma of the breast: Past, present, and future. Front. Oncol. 2024;14:1435421. doi: 10.3389/fonc.2024.1435421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Zhao T., Liu C., Xing H. Male invasive breast carcinoma containing both mucinous and micropapillary components with axillary lymph node metastasis: A rare case report with literature review. Gland. Surg. 2026;15:27. doi: 10.21037/gs-2025-417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Page D.L., Dixon J.M., Anderson T.J., Lee D., Stewart H.J. Invasive cribriform carcinoma of the breast. Histopathology. 1983;7:525–536. doi: 10.1111/j.1365-2559.1983.tb02265.x. [DOI] [PubMed] [Google Scholar]
- 25.Emiroglu S., Abuaisha A.M., Tukenmez M., Cabioglu N., Bayram A., Ozmen V., Muslumanoglu M. Pure Tubular Breast Carcinoma: Clinicopathological Characteristics and Clinical Outcomes. Eur. J. Breast Health. 2023;19:115–120. doi: 10.4274/ejbh.galenos.2023.2022-12-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Vermeulen M.A., Slaets L., Cardoso F., Giordano S.H., Tryfonidis K., van Diest P.J., Dijkstra N.H., Schroder C.P., van Asperen C.J., Linderholm B., et al. Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Eur. J. Cancer. 2017;82:219–227. doi: 10.1016/j.ejca.2017.01.034. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.