Breast Cancer screening biopsies: Risk of Underestimation

"Underestimation" refers to a premature conclusion that a lesion is not serious, which later turns out to be quite serious. Attending physicians always try to balance the need for accurate and reliable diagnositic information, with the inconvenience and strain placed on the body when obtaining that information. In the case of follow-up biopsies following a suspicious mammogram, the quetion becomes whether to use the least invasive 'fine needle' aspiration, core biopsies ( also with needle extraction ) with or without vaccuum assistance, or open surgical excision. The most serious underestimation is when a lesion is diagnosed as ADH or atypical ductal hyperplasia, which later appears to have been DCIS.

Atypical Ductal Hyperplasia (ADH) is the most frequently underestimated condition with biopsies.

Stereotactic core needle biopsies are probably the most common means of evaluating nonpalpable ammographic abnormalities. Core biopsies have proven to be very sensitive indicators of present invasive cancer, but far less reliable in distinguishing between the less serious conditions. For patients who were initially given a diagnosis of atypical ductal hyperplasia following a core biopsy, it is not uncommon to have the diagnosis upstaged to breast cancer after an excisional biopsy. Some studies show the underestimation rate to be about 17%. However, there appears to be no correlation between the number of core samples taken and diagnostic accuracy.

The most probable reason for the underestimation is that limited tissue available in core biopsy specimens may show qualitative changes in DCIS, but not enough quantity of change for a devinitive diagnosis. Another explanation is simply that low grade, smaller size lesions are much more difficult to visualize on the imaging studies.

Upgrade risk to breast cancer for various types of cellular atypia

Pathologists have found different rates of upgrade to breast cancer for different types of breast atypia, but the range is still between 10-20%. Atypical ductal hyperplasia (ADH) is upgraded about 20% of the time, , atypical lobular hyperplasia (ALH- occuring in the breast lobules) about 10% , and flat epithelial atypia (FEA) upgraded about 17%.

Excisional biopsies are much more inconvenient and stressful for women, so the question becomes whether or not the risk of underestimated breast cancer is worth trouble. While there is still some variability of opinion, there appears to be a growing consensus that an excisional biopsy should be performed after all diagnosis of ADH. (ALH and FEA are not to be discounted, but underestimation rates seem to be just below the 'risk-threshold' for requiring an excisional biopsy instead of just core biopsies.)

Risk of 'underestimation' of breast cancer risk due to insufficient sampling

The underestimation rate for all biopsies is influenced by the number of specimens taken, the type of procedure, and the sampling site. Microcalcifications are associated with DCIS. They tend not to be found in tissues from an invasive tumor, but rather from areas of DCIS and adjacent benign tissue. So, by restricted biospy tissue samples to the tumor site only, it is quite possible to miss carcinoma developed from benign or undiscovered DCIS areas.

There is some correlation between the gauge of the needle with or without vacuum assistance, and the tendency to underestimate or 'miss' the detection of malignancy. For example, microcalcifications can be missed because they tend to occur in areas of DCIS, or in adjacent benign tissue, rather than in the invasive tumor itself. What we see then, is tendency for misdiagnosis, albeit only for a short time, in which atypical ductal hyperplasis (ADH) is eventually upgraded to DCIS, or in which DCIS is eventually upgraded to invasive carcinoma.

The table below summarizes this statistical tendency for 'underestimation' for the different needle gauges with or without vacuum assistance.

	Large core biopsy, 14 gauge.	directional vacuum assisted biopsy, 14 gauge.	directional vacuum assisted biopsy, 11 gauge.
Upgrade of ADH to DCIS	48%	28%	17%
Upgrade of DCIS to invasive carcinoma	25%	15%	11%

The chances of an underestimation in the histological workup of a percutaneous biopsy is minimized with the 11 gauge vacuum assisted technique.

Underestimation rates between excisional biopsy and 11 guage VAD are similar

It is noteworthy that the underestimation rate of DCIS becoming invasive breast cancer is not significantly different that the underestimation rate of excisional biopsy ( preceded by neelde localization). 11 guage VAD biopsies underestimate DCIS about 16% of the time, while the underestimation rate for guided excision biopsies is about 11%.

Overall underestimation rates of breast cancer screening/staging biopsies

Even when an 'imaging target' ( a desired sample area based on the mammgram, ultrasound, or MRI) is completely excised, the underestimation of atypical cell growth sill occurs between 10% and 27% of the time. Even when all 'visual' evidence of possible a possible breast cancer lesion was completely removed with the 11 guage-VAD biopsy, subsequent surgical excision still reveals residual cancer in between about 50-72% of patients. For this reason, surgical excision is just about always warranted when a 'stereotactic' biopsy ( where the exact position of the desired biopsy sample has been calculated from multiple image views) has revealed atypical ductal hyperplasia and/or DCIS, whether or not a residual lesion is present on the imaging studies.

Fine needle aspiration has trade-offs in finding breast cancer

If the suspected breast cancer lesion appears to be of high cellular content because it is already 'solid', many radiologists and pathologists prefer the fine needle biopsy. This approach is much less invasive, but less representative. It is not possible to distinguish between infiltrating carcinoma and DCIS, for example.

Core Biopsies are very accurate for invasive breast cancer, but not so for DCIS

It would seem that no method of core biopsy currently available is sensitive enough to completely reassure surgeons that an excisional biopsy is not required, when an atypical intraductal epithelial proliferation is found at the core. However, it should be noted that on the whole core biopsies are still of considerable value in the managment of DCIS, and can reduce the number of surgical operations by up to 30%.

Overall we are reminded that both benign and atypical findings on core biopsy samples, when accompanied by radiological features suspicious of DCIS, should be investigated further.

To investigate the accuracy of core biopsy in the diagnosis of cancer in patients with DCIS.

Conclusion: Although core biopsies are highly accurate forms of obtaining a preoperative diagnosis in patients with invasive breast cancer, this is not the case in DCIS.

Core biopsy was attempted in 88% (81/92) of patients with DCIS and in 91% (874/959) of those with invasive disease. Of those patients who underwent core biopsy, a diagnosis of carcinoma on the initial core was made in 65% (53/81) of patients with DCIS compared with 92% (800/874) of patients with invasive disease (p<0.0001). Smaller lesion size (p?=?0.005) and lower grade (p?=?0.03) were associated with increased risk for a negative or non-diagnostic core in patients with DCIS. The nature of the mammographic lesion or the method of biopsy did not affect the probability of an accurate core biopsy. Patients who had a preoperative diagnosis of DCIS by core biopsy had a reoperation rate of 36% compared with 65% of those that did not have a preoperative diagnosis (p?=?0.007).

References

Lee, CH. Philpotts, LE., Tocino, I.; Follow-up of breast lesions diagnosed as benign with stereotactic core-needle biopsy: frequency of mammographic change and false-negative rate. Radiology 1999;212-194
L.W.Bassett, S.A.Feig, R.E.Hendrick,V.P.Jackson, E.A.Sickles, Breast Disease (third series) test and syllabus ACR 2001. S.A.Feig, p122-215
Lee C, Carter D, Philpotts L et al, Ductal Carcinoma in Situ Diagnosed with Stereotactic Core Needle Biopsy: Can Invasion Be Predicted? Radiology Nov. 2000;217: 466-470
Winchester, DJ., Bernstein, JR., Jeske, JM., Nicholson, MH., Hahn, EA., Goldschmidt, RA., Watkin, WG., Sener, SF., Bilmoria, MB., Barrera, E., Winchester, DP.;Upstaging of Atypical Ductal Hyperplasia After Vacuum-Assisted 11-Gauge Stereotactic Core Needle Biopsy. Arch Surg. 2003;138:619-623.
Eby, PR., Ochsner, JE., DeMartini, WB., Allison, KH., Peacock, S. Lehman, CD.; Frequency and Upgrade Rates of Atypical Ductal Hyperplasia Diagnosed at Stereotactic Vacuum-Assisted Breast Biopsy: 9-Versus 11-Gauge. AJR 2009; 192:229-234
Darvishian, F., Singh, B., Simsir, A., Ye, W., Cangiarella, JF., Atypia on Breast Core Needle Biopsies: Reproducibility and Significance. Annals of Clinical & Laboratory Science 39:270-276 (2009)
Dillon, MF., Quinn, CM., McDermott, EW., O'Doherty, A., O'higgins, N., Hill, ADK.; Diagnostic accuracy of core biopsy for ductal carcinoma in situ and its implications for surgical practice. J Clin Pathol 2006;59:740-743
Parker SH, Klaus AJ, Performing a breast biopsy with a directional, vacuum-assisted biopsy instrument RadioGraphics 1997;17:1233-1252.
Burbank F. Stereotactic breast biopsy of atypical ductal hyperplasia and ductal carcinoma in situ lesions: improved accuracy with a directional, vacuum-assisted biopsy instrument. Radiology 1997; 202: 843-847.
Liberman L, Gougoutas CA, Zakowski MF, LaTrenta LR, Abramson AF, Morris EA, Dershaw DD, Calcifications highly suggestive of malignancy: comparison of breast biopsy method. AJR:177,165-172, July 2001.

Back to breast cancer screening list.