How Big Is 2.1 Cm

• Journal List
• Curr Oncol
• v.xx(four); 2013 Aug
• PMC3728051

Curr Oncol. 2013 Aug; xx(4): 205–211.

Are two-centimeter breast cancers large or minor?

S.A. Narod, MD, ^* J. Iqbal, MD,^* A. Jakubowska, PhD,^† T. Huzarski, Doc PhD,^† P. Sun, PhD,^* C. Cybulski, Physician PhD,^† J. Gronwald, MD PhD,^† T. Byrski, MD PhD,^† and J. Lubinski, Doc PhD^†

S.A. Narod

^*Women's College Research Plant, Academy of Toronto, Toronto, ON.

J. Iqbal

^*Women'due south Higher Research Plant, University of Toronto, Toronto, ON.

A. Jakubowska

^†International Hereditary Cancer Heart, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

T. Huzarski

^†International Hereditary Cancer Middle, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

P. Sun

^*Women's Higher Research Institute, Academy of Toronto, Toronto, ON.

C. Cybulski

^†International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

J. Gronwald

^†International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

T. Byrski

^†International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

J. Lubinski

^†International Hereditary Cancer Center, Section of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

Abstract

Background

Node-negative breast cancers from two cm to 5 cm in size are classified equally stage ii, and smaller cancers, as phase i. We sought to make up one's mind if the prognosis of women with a breast cancer exactly 2 cm in size more than closely resembles that of women with a phase i or a stage 2 breast cancer.

Methods

Using a cohort of 4265 young women with breast cancer, we compared the x-year chest cancer mortality rates for women who had a tumour 0.one–i.9 cm, exactly 2.0 cm, and 2.1–2.9 cm.

Results

In the starting time 3 years afterwards diagnosis, the survival pattern of women with a 2.0-cm chest cancer was nearly identical to that of women with a larger cancer (2.i–iii.0 cm). From year iii to year 10, the relative survival of women with a ii.0-cm breast cancer was improved and nearly identical to that of women with a smaller cancer. The 10-year survival rate was 89.three% for women with tumours less than 20 mm, 86.1% for women with tumours equal to 20 mm, and 81.two% for women with 21-mm to 29-mm tumours.

Conclusions

For young women with small breast cancers, the relative mortality from chest cancer is dynamic with increasing neoplasm size and varies with time from diagnosis.

Keywords: Breast cancer, stage, survival

1. INTRODUCTION

Cancers of exactly 2 cm in size occupy a special niche in chest oncology. That size is the one at which breast cancer is most commonly diagnosed (the "modal size") and 2.0 cm marks the boundary between stage i and two for node-negative breast cancers and between stage ii and iii for node-positive breast cancers. The size of the primary tumour and the nodal status are the ii most useful parameters for predicting prognosis in breast cancer patients and for planning clinical management. In patients who present with localized breast cancer, increasing tumour size is inversely correlated with breast cancer–specific survival^{one – 5}.

Conventionally, neoplasm size is measured by the pathologist based on the largest diameter of the resected specimen, estimated to the nearest millimetre. Nevertheless, size evaluation is inexact, and pathologists tend to round the neoplasm size to the nearest centimetre or half-centimetre. Every bit a result, many tumours are reported to exist 2.0 cm in size, but relatively few are reported to be 1.9 cm or 2.1 cm. Because 2.0-cm breast cancers represent a big proportion of all breast cancer patients, and because 2.0 cm defines the edge between stage i and ii breast cancers, a detailed examination of the clinical class of those tumours is of interest. We examined size distribution and tumour characteristics in 4265 unselected breast cancer patients diagnosed at age l or younger. Nosotros compared the 5- and ten-year survival rates and annual mortality rates for young women with cancers whose size was reported to be exactly 2.0 cm and compared those rates with the rates for women with smaller and larger cancers.

ii. METHODS

We studied a cohort of 5502 women with invasive chest cancer who were treated between 1995 and 2008 at one of seventeen clinical centres affiliated with the Pomeranian Medical University of Szczecin, Poland. All patients were 50 years of age or younger at diagnosis. Clinical characteristics were retrieved from the medical records: age at diagnosis, tumour size, lymph node involvement (yes, no); estrogen receptor (er)–status (positive, negative, missing); progesterone receptor status (positive, negative, missing) and her2 (human epidermal growth factor receptor 2) condition (positive, negative, missing).

The neoplasm size was recorded in millimetres and was taken equally the greatest dimension of the neoplasm determined by pathology test. For the purposes of the present study, tumour size was stratified every bit follows:

• Tumours of ane–19 mm

• Tumours equal to xx mm

• Tumours of 21–xxx mm

For the assay, nosotros restricted the written report sample to 4265 patients with a neoplasm size less than or equal to 30 mm, which included 85% of the patients in the database. Follow-up of patients has been maintained by periodic review of medical charts and by phone contact with individual patients. For deceased patients, the date and cause of expiry were recorded.

2.ane. Statistical Methods

Descriptive statistics were used to calculate frequencies of variables for patients in the 3 tumour-size categories. The means were compared using the Pupil t-test, and frequency distributions across the three neoplasm-size categories were compared using the chi-foursquare test. A survival analysis was conducted for the 4265 patients. Survival was defined as fourth dimension from the diagnosis of breast cancer until death from breast cancer, expiry from a non-chest-cancer cause, death from an unknown crusade, or date of last contact. The Kaplan–Meier method was used to estimate overall survival. The log-rank test used to test the significance of the differences in survival between groups. A Cox multivariate analysis was used to evaluate the effect of tumour-size category on chest cancer mortality subsequently adjusting for age (years), er condition (positive or negative), and nodal condition (positive or negative). Nosotros also compared the almanac mortality rates for women with cancers in the three groups over the first 10 years after diagnosis and adamant the times at which the bloodshed rate peaked. The Statistical Analysis Arrangement (SAS, version ix.1.3: SAS Institute, Cary, NC, U.S.A.) was used for all analyses.

three. RESULTS

Effigy 1 presents the distribution of sizes for the primary tumours in the study accomplice. The distribution is not polish; information technology represents rounding by the pathologists. The patients were then stratified by tumour size: 2635 cancers (61.eight%) were 0.1–i.9 cm; 629 cancers (xiv.7%) were 2.0 cm, and 1001 cancers (23.5%) were 2.1–2.9 cm.

Neoplasm-size distribution of breast cancers.

Table i presents the baseline clinical characteristics of the patients in the three groups. Mean age at diagnosis was like across the three tumour categories. Compared with smaller tumours, larger tumours were associated with a greater probability of lymph node involvement; they were also more probable to be er-negative and to have been treated with mastectomy.

Table I

Baseline characteristics of patients by the size of principal tumour

Feature	Tumour size			p Value
	ane–xix mm	twenty mm	21–30 mm
Patients (n)	2635	629	1001	—
Age
Hateful	44.3	44.2	44	0.64
Range	21–50	26–50	19–50
Nodal status [north (%)]
Node-positive	914 (37.2)	293 (49.3)	534 (55.7)	<0.00001
Node-negative	1544 (62.eight)	301 (l.seven)	424 (44.iii)
er status [n (%)]
Positive	1538 (64.seven)	341 (61.8)	508 (55)	<0.00001
Negative	839 (35.3)	211 (38.two)	416 (45)
hertwo status [n (%)]
Positive	244 (15.5)	78 (21.6)	124 (eighteen.vii)	0.01
Negative	1326 (84.five)	283 (78.4)	541 (81.iv)
Breast surgery [n (%)]
Lumpectomy	595 (29.1)	70 (14.6)	xc (11.9)	<0.0001
Mastectomy	1447 (70.9)	411 (85.five)	666 (88.1)
Radiotherapy [northward (%)]
Yep	1176 (56.8)	271 (54.ix)	459 (58)	0.54
No	893 (43.2)	223 (45.one)	332 (42)
Radiotherapy amongst lumpectomy patients [n (%)]
Yeah	500 (90.nine)	59 (89.four)	79 (95.ii)	0.37
No	50 (nine.one)	7 (ten.six)	4 (4.eight)
Chemotherapy [n (%)]
Yes	1653 (74.9)	477 (88.viii)	806 (94.two)	0.0001
No	553 (25.1)	60 (eleven.2)	50 (5.8)
Death [n (%)]	239 (nine.1)	77 (12.two)	164 (sixteen.4)	0.001

Mean follow-upwardly was 7.vii years (range: 0–16 years). Over the 10-year follow-up catamenia studied, 480 deaths from chest cancer were recorded amid the 4265 patients (11.3%). The five-year overall survival was 95.iii% for patients with tumours less than 20 mm in size, 91.9% for patients with tumours equal to 20 mm, and 89.5% for patients with tumours 21–30 mm (p < 0.0001, Figure 2). All the same, at 10 years, the survival of women with chest cancers of ii.0 cm was similar to that of women with smaller cancers (89.three% for patients with tumours <20 mm, 86.one% for patents with 20-mm tumours, and 81.ii.% for patients with tumours 21–29 mm).

Survival by tumour size, 0–10 years.

The difference in survival patterns is credible when the ten-year follow-upward menstruation is inspected closely (Figure 2). In the first 3 years later on diagnosis, the survival bend for 2.0-cm breast cancers tracks with the larger cancers (Figure three). In the period from three to x years, the 2.0-cm cancers track with the smaller cancers (Figure 4). We confirmed those differences in a statistical model, using a Cox proportional hazards assay of survival and dividing the follow-up catamenia into two. Tabular array ii presents the results of the univariable and multivariable analyses. In the adjusted analysis, the hazard ratio for ii.0-cm cancers compared with smaller cancers was 1.51 in the starting time 3 years (95% confidence interval: one.01 to 2.27) and 1.04 for years 3 to ten (95% confidence interval: 0.74 to 1.45). In contrast, the event of nodal condition on prognosis was similar for the two time periods. The survival reward for er-positive patients was apparent in the two time periods, merely adulterate with time (Tabular array ii ).

Survival past tumour size, 0–3 years.

Survival by tumour size, 3–10 years.

Table II

Hazard ratios for bloodshed associated with tumour size and other prognostic factors, by time since diagnosis

Variable	Menstruation of analysis
	Diagnosis to 3 years						3 to 10 years
	Unadjusted			Adapted			Unadjusted			Adjusted
	hr	95% ci	p Value	hr	95% ci	p Value	hr	95% ci	p Value	hour	95% ci	p Value
Age	0.97	0.95 to 1.00	0.05	0.98	0.95 to 1.01	0.eleven	0.97	0.95 to 0.99	0.004	0.97	0.95 to 0.99	0.007
Neoplasm size
ane–xix mm	1.0			i.0			ane.0			1.0
20 mm	one.73	1.15 to 2.69	0.008	one.51	1.01 to 2.27	0.05	1.18	0.84 to 1.65	0.33	1.04	0.74 to ane.45	0.82
21–29 mm	ii.05	i.47 to 2.86	0.0001	1.59	1.fourteen to 2.23	0.006	ane.89	ane.47 to two.43	0.0001	1.55	1.21 to ii.00	0.0006
Nodal status
Negative	1.0			1.0			one.0			1.0
Positive	iii.53	2.55 to four.89	0.0001	3.38	2.43 to four.seventy	0.0001	iii.48	2.71 to 4.46	0.0001	3.31	2.58 to 4.25	0.0001
er status
Negative	one.0			ane.0			1.0			1.0
Positive	0.27	0.20 to 0.38	0.0001	0.28	0.20 to 0.forty	0.0001	0.68	0.54 to 0.86		0.70	0.55 to 0.88	0.002

Amongst the 4265 patients, 2269 had node-negative cancer, and 1741 had node-positive cancer. The shift from poor prognosis to practiced prognosis at year 3 or thereabouts was particularly evident in the node-positive cancers (Figure 5). Figure 6 presents the experience of the 501 patients with triple-negative cancers. In this subgroup, the survival experience for women with cancers of all sizes was like for the first ii years; thereafter, the intermediate-size (two.0-cm) cancers tracked with the smaller cancers.

Survival by tumour size, 0–10 years, node-positive disease only.

Survival by tumour size, 0–ten years, triple-negative disease only.

Table 3 and Figure 7 present the almanac expiry rate for all patients in the three neoplasm-size categories.

TABLE III

Annual bloodshed rate, by time since diagnosis and neoplasm size

Variable	Annual mortality rate (%)
	Years one–5	Years five–10
Tumour size
1–19 mm	1.thirteen	1.20
twenty mm	1.79	1.25
21–29 mm	ii.42	one.97

Annual mortality afterwards breast cancer, by tumour size, all subjects.

4. DISCUSSION

In this study, we closely examined the relationship between tumour size and survival in young women with small breast cancers. Our database was large (4265 patients), and we were able to consider women with tumours of exactly ii.0 cm as a single category. Currently, such cancers (if node-negative) are classified as stage i breast cancers. Not surprisingly, the clinical outcome in women with such tumours was intermediate between those in the stage i and stage ii groups as a whole, but the departure was qualitative as well every bit quantitative. Over the ten-twelvemonth follow-up period, the relative survival of women with 2.0-cm cancers improved with respect to women having smaller cancers. However, in the start iii years afterward diagnosis, the survival of women with 2.0-cm cancers was significantly worse than that for women with smaller cancers (hazard ratio: ane.73; 95% conviction interval: 1.15 to 2.69; p = 0.008).

Our study illustrates that, in survival analyses, if the hazard ratio is erroneously causeless to be proportional over time, it is possible to overlook subtle differences in upshot. This observation has clinical relevance and also raises important questions about the natural history of chest cancer. Nosotros propose that, for women with small breast cancers, changes in size attributable to screening or to improved sensation might have different clinical effects at different time points afterward diagnosis. To ensure that a clinical study is reliable, it is important that nigh patients exist followed for a long period, ideally for 10 or more years. Studies based on shorter follow-up periods (v years, say) may lead to erroneous conclusions even if the total number of person–years is large—a state of affairs similar to that with ovarian cancer^{6 , 7}. Screening studies and studies involving clinical interventions tin can both potentially be affected.

A second effect relates to the biologic basis for our observations. It is possible that the adverse impact of 2.0-cm tumours compared with smaller ones relates to the relative proportions of one or more adverse prognostic factors in the diverse subgroups at diverse times after diagnosis. The information are consistent with a prognostic cistron that has a negative impact on survival for iii years merely and that is more mutual in cancers of ii.0 cm than in larger cancers. For example, the adverse prognosis associated with triple negativity is full-bodied in years 0–five; thereafter, recurrence rates are similar to or less than those of er-positive cancers^eight. Our report merged all patients with triple-negative breast cancer because nosotros lacked data on other relevant markers such every bit epidermal growth factor receptor and cytokeratins 5 and 6. Information technology is possible that, within the triple-negative phenotype, certain subgroups have different patterns of mortality. The expectation is that, if a prognostic cistron increases mortality, the proportion of cases positive for that cistron reject with time from diagnosis. Positive nodal status had an adverse effect on survival at all time points (Table ii ), and the fraction of node-positive cancers declines with time elapsed (Effigy 8). At diagnosis, er-positivity is a skillful prognostic feature, simply it adversely affects outcomes later on⁹. That attenuation is axiomatic in Table 2 . As predicted, the prevalence of er-positive cancers rose from yr ane to year 5 and then declined from year v to year x (Figure 9).

Proportion of node-positive subjects, by years elapsed since diagnosis.

Proportion of estrogen receptor (er)–positive subjects, past years elapsed since diagnosis.

These observations besides enhance interesting questions about the nature of breast cancer progression. According to the basic model, patients who dice of chest cancer are among those in whom latent metastases (residual illness), nowadays subsequently breast surgery completion, fail to be afterwards eradicated by adjuvant chemotherapy. In its simplest form, the model predicts that the probability of death is proportional to the probability that viable residuum metastases are nowadays after handling. If in-breast neoplasm size alone were an indicator of the probability that latent metastases are present, then the curves in Figure 2 would be expected to be parallel. The data suggest that the model is more complex—that is, that the initial measured size of the neoplasm influences survival in other ways. For example, it might correlate with the intrinsic metastatic growth rate. The probability of dying in a given time interval after diagnosis is a reflection of the extent of viable residual disease, the fourth dimension to afar recurrence (growth rate), and the fourth dimension from distant recurrence to death. In support of this proposition is the observation that the time from diagnosis to local recurrence is highly correlated with the time from recurrence to death¹⁰.

Here, we focus on neoplasm size, admitting inside a narrow clinical range, and we extend the findings of others that the statistical effect of neoplasm size on cancer recurrence is contingent on the presence or absence of other relevant prognostic features. In the past decade, several studies of gene expression profiles have improved our ability to predict distant relapse and expiry, merely fifty-fifty when expression profiles are included, tumour size retains its independent predictive ability^{11 , 12}. The relationship is attenuated for triple-negative cancers^{13 , 14} and for BRCA1-associated breast cancers^xv. Furthermore, neoplasm size may influence survival differently according to lymph node status, but that contingency may not be fully captured if nodal status is dichotomized. Among node-positive patients, 5-year survival was seen to be similar for the two.0-cm tumours and the tumours of 2.ane–three.0 cm. In a contempo commodity, Wo et al. ¹⁶ report that, amongst women with 4 or more positive nodes, those with very modest breast cancers had a much worse prognosis than would have been predicted from the size of their tumours. Similarly, very large tumours that are node-negative may be represent a biologically indolent phenotype¹⁷.

5. CONCLUSIONS

We found that the survival feel of women with a ii.0-cm breast cancer neoplasm was like to that of women with larger cancers for 3 years and that their survival then tracked that of women with smaller cancers from year 3 to year 10. That observation raises interesting questions nigh the biologic underpinnings of the dynamic nature of prognostic factors over time.

half-dozen. CONFLICT OF INTEREST DISCLOSURES

All authors declare no fiscal conflicts of involvement.

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How Big Is 2.1 Cm,

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728051/

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