Comparative pathology of breast cancer in a randomised trial of screening

Anderson, T. J.; Lamb, Joanne; Donnan, Peter T.; Alexander, Freda E.; Huggins, Alison; Muir, B. B.; Kirkpatrick, A. E.; Chetty, U.; Hepburn, W.; Smith, Andrew J.H.

doi:10.1038/bjc.1991.251

Cited by 75 publications

(29 citation statements)

References 22 publications

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“…The current investigation confirms one observation reported by Anderson et al (1991). In a case series from the Edinburgh Randomised Breast Screening Project, SD cancers had a crude (univariate) advantage in the frequency of positive lymph nodes that decreased progressively from pT1a to pT1c lesions.…”

Section: Discussionsupporting

confidence: 79%

“…Owing to the paucity of such cases (Table 1), their behaviour might be subject to random variation. A similar observation, however, was also reported from the Edinburgh Randomised Breast Screening Project (Anderson et al, 1991). The hypothesis we raise points to the fact that most years of screening covered by this study were the initial years of each local programme.…”

Section: Discussionmentioning

confidence: 56%

“…Starting from the universal observation that the average risk of lymph node involvement is lower for SD breast cancer cases compared with clinically diagnosed cases, the rationale of the current study was based on the following assumptions: (1) axillary lymph node status is the product of biological aggressiveness and chronological age of the disease (Mittra and MacRae, 1991), (2) for any breast cancer case, tumour size is an indicator of its chronological age, and (3) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time (Anderson et al, 1991;Norden et al, 1997;Ernst et al, 2002). We evaluated the tumour size-specific risk of lymph node involvement for SD cases relative to that for clinical cases.…”

Section: Rationalementioning

confidence: 99%

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Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Bucchi

Barchielli²,

Ravaioli

et al. 2004

Br J Cancer

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Screen-detected (SD) breast cancers are smaller and biologically more indolent than clinically presenting cancers. An often debated question is: if left undiagnosed during their preclinical phase, would they become more aggressive or would they only increase in size? This study considered a registry-based series (1988 -1999) of 3329 unifocal, pT1a-pT3 breast cancer cases aged 50 -70 years, of which 994 were SD cases and 2335 clinical cases. The rationale was that (1) the average risk of lymph node involvement (N þ ) is lower for SD cases, (2) nodal status is the product of biological aggressiveness and chronological age of the disease, (3) for any breast cancer, tumour size is an indicator of chronological age, and (4) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time. The hypothesis was that the relative protection of SD cases from the risk of N þ and, thus, their relative biological indolence decrease with increasing tumour size. The odds ratio (OR) estimate of the risk of N þ was obtained from a multiple logistic regression model that included terms for detection modality, tumour size category, patient age, histological type, and number of lymph nodes recovered. A term for the detection modality-by-tumour size category interaction was entered, and the OR for the main effect of detection by screening vs clinical diagnosis was calculated. This increased linearly from 0.05 (95% confidence interval: 0.01 -0.39) in the 2 -7 mm size category to 0.95 (0.64 -1.40) in the 18 -22 mm category. This trend is compatible with the view that biological aggressiveness of breast cancer increases during the preclinical phase.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 56%

Section: Rationalementioning

confidence: 99%

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Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Bucchi

Barchielli²,

Ravaioli

et al. 2004

Br J Cancer

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“…7 Several reports indicate that breast cancers detected by screening have more favorable pathological features compared with symptomatic breast cancers, some of which may be due to a stage shift, and some to underlying biological differences. [8][9][10] In addition to stage shift and length bias or overdiagnosis, there is an artificial increase in survival due to lead time (if screening detects a tumor on average 3 years earlier than symptoms would have arisen, 3 years are added to the survival time regardless of the eventual outcome).…”

mentioning

confidence: 99%

Prognosis and pathology of screen‐detected carcinomas

Nagtegaal

Allgood

Duffy³

et al. 2010

Cancer

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BACKGROUND: It has been observed that screen-detected breast cancers have a better prognosis than symptomatic tumors, even after taking pathological tumor attributes into account. This has led to the hypothesis that screendetected tumors are substantially biologically different from symptomatic cancers. METHODS: The pathology and survival by detection mode was investigated in 21,382 breast cancers diagnosed in women aged 50-64 years in the West Midlands, United Kingdom, between 1988 and. Tumor attributes were compared using chi-square tests and logistic regression. Survival was analyzed using Cox regression. RESULTS: Screen-detected cancers were significantly smaller, better differentiated, and less likely to be node-positive than symptomatic cancers (P < .001 in all cases). In addition, a higher proportion of screen-detected cancers were hormone receptor-positive, and a higher proportion were tubular carcinomas (P < .001). Survival was substantially better in screen-detected breast cancers (86% at 10 yearsvs 70% for interval cancers and 58% for cancers in women unexposed to screening). Adjustment for age, tumor size, nodal status, grade, histological type, and year of diagnosis accounted for 64% (interval cancers) and 68% (unexposed women) of these survival differences, respectively. Overall survival improved with time. Approximately half of this improvement was due to the increase over time in the proportion of tumors that were screendetected. CONCLUSION: The majority of the difference in prognosis between screen-detected and symptomatic breast cancers is due to the differences in routinely measured pathological features (size, type, grade, and nodal status), leaving a small residual difference to be accounted for by other biological differences.

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“…The detected cancers are smaller in size and thus have lower pathologic T stage, the frequency of regional lymph node metastases is lower, and more cancers are detected at preinvasive stage. 1,2 These changes triggered a cascade evolution of breast cancer treatment from radical mastectomy with radiation therapy and lymph node dissection to less debilitating and more cosmetically acceptable procedures of breast-conserving therapy. 3,4 Nipple-sparing mastectomy (NSM) is a variant of breast-sparing mastectomy performed in patients with minimal risk of nipple involvement by carcinoma to preserve this important anatomic structure for consecutive breast reconstruction.…”

mentioning

confidence: 99%

Prevalence of Terminal Duct Lobular Units and Frequency of Neoplastic Involvement of the Nipple in Mastectomy

Kryvenko

Yoon

Chitale

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.—Breast cancer treatment has greatly evolved from radical mastectomy to more cosmetically acceptable and less-debilitating surgeries. Nipple-sparing mastectomy is increasingly done for both cancer treatment and risk reduction. The frequency of terminal duct lobular units (TDLUs) and occult neoplastic epithelial proliferation in grossly/clinically unremarkable nipples (GUNs) is not well investigated. Objective.—To describe frequency of TDLUs and occult and overt neoplastic nipple involvement. Design.—Nipples from 105 consecutive specimens (90 therapeutic, 15 prophylactic) were studied. Sixty-five nipples were entirely submitted to evaluate frequency of TDLUs; the rest had 1 vertical section submitted. Results.—Terminal duct lobular unit was seen in 17 GUNs (26%). Six had TDLU in the base, 6 had it in the papilla, and 5 in both. Four GUNs showed lobular carcinoma in situ (1), Paget disease (1), and pagetoid extension of underlying malignancy (2). Grossly/clinically abnormal nipples had Paget disease (2), lymphovascular invasion (2), invasive carcinoma (4), and pagetoid extension (5). Involved nipples were closer to tumor (mean, 1.1 versus 3.2 cm, P < .001), had larger underlying tumors (mean, 4.3 versus 2.6 cm, P = .03) and of higher grade (P = .04), and more often had lymph node metastases (91% versus 44%, P = .007). No pathologic abnormalities were found in prophylactic mastectomy nipples. Conclusions.—Terminal duct lobular units were seen in 26% of nipples. They were frequently seen in the nipple papilla. Occult neoplastic epithelial proliferation was seen in 5% of grossly/clinically unremarkable therapeutic mastectomy nipples. Pagetoid extension was the dominant spread of underlying malignancy. Overall, the nipple was more often involved by larger and higher-grade tumors located closer to the nipple. All prophylactic mastectomies had unremarkable nipples. These findings should be considered while selecting patients for nipple-sparing mastectomy.

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Comparative pathology of breast cancer in a randomised trial of screening

Cited by 75 publications

References 22 publications

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Prognosis and pathology of screen‐detected carcinomas

Prevalence of Terminal Duct Lobular Units and Frequency of Neoplastic Involvement of the Nipple in Mastectomy

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