Use of Fine Needle Aspiration for Solid Breast Lesions Is Accurate and Cost#Effective

Mark Rubin, MD, Kent Horiuchi, BS, Nancy Joy, MD, William Haun, MD, Robert Read, MD, Erick Ratzer, MD, Michael Fenoglio, MD, Denver, Colorado

BACKGROUND: Palpable breast tumors have tradi- tionally been diagnosed with open biopsy or core biopsy. We propose fine needle aspiration biopsy (FNA) as a reliable, cost-saving initial procedure in these patients.

METHODS: Eighty-five palpable solid breast masses of the breast in 86 patients were classi- fied by a combination of physical examination, mammography, and/or ultrasound as probably benign, indeterminate, or highly suspicious for cancer. All tumors had FNA biopsies. All patients had either a confirmatory open biopsy (66) or close clinical follow-up (30) with a mean follow- up of 29 months (range 6 to 36).

RESULTS: Thirty-four patients classified as clini- cally benign had a benign FNA biopsy. No can- cers were detected in this group by either open surgical biopsy or clinical follow-up. Twenty pa- tients were classified clinically as indeterminate. All had FNA biopsies, and 6 were either positive for cancer or suspicious for cancer. Fourteen pa- tients had negative FNA biopsies. Five of the 6 abnormal biopsies had cancer on open biopsies. The 1 false-positive result occurred in a lactating patient. Thirty-one patients were classified clini- cally as highly suspicious for cancer. Twenty- three were confirmed as cancer with FNA biopsy. Eight needed open surgical biopsy to confirm cancer. All 31 patients clinically suspicious for cancer had cancer. In patients classified clinically as highly suspicious or probably benign, FNA was a reliable first diagnostic step (100% positive pre- dictive value, 100% specificity, 87% sensitivity, and 89% negative predictive value).

CONCLUSIONS: Fine needle aspiration biopsy of solid palpable breast lesions should be the diag- nostic procedure of choice for those patients classified clinically as probably benign or clini- cally as highly suspicious for cancer. Cost analy- sis revealed elimination of an open biopsy in such cases would save $1,100 per patient. For highly suspicious cases, a negative fine needle aspira- tion should not deter an open surgical biopsy. For

From the Department of Surgery, St. Joseph Hospital, Denver, Colorado.

Requests for reprints should be addressed to Mark Rubin, MD, Department of Surgical Education, St. Joseph Hospital, 1835 Franklin, Denver, Colorado 80218.

Presented at the 49th Annual Meeting of the Southwestern Sur- gical Congress, Ranch0 Mirage, California, April 13-l 6, 1997.

patients classified as indeterminate, fine needle aspiration biopsy results are not reliable enough to determine treatment. Am J Surg. 1997;174:694-698.0 1997 by Excerpta Medica, Inc.

P

hysical examination, mammography and/or ultra- sound, fine needle aspiration (FNA) and open surgi- cal biopsy are firmly established in the diagnosis of

patients with palpable breast masses.lm4 The reliability of these tests has been documented in multiple reports, and they are routinely employed in the preoperative assessment of any woman who presents with a palpable breast mass. The combination of physical examination, mammography and/or ultrasound, and open surgical biopsy has been shown to be highly accurate in making the correct diagnosis.

We set out to determine if fine needle aspiration biopsy along with physical examination and mammography and/ or ultrasound could be used to avoid open surgical biopsy in patients with palpable solid breast masses and to deter- mine if this would be a more cost-effective means of diag- nosis.

METHODS Eighty-five women with 85 palpable solid breast masses

were classified by a combination of physical examination, mammography, and/or ultrasound as either probably be- nign, indeterminate, or highly suspicious for breast cancer. All tumors had fine needle aspiration biopsy. Lesions were classified as highly suspicious if two of the three above methods of clinical evaluation classified the lesion as sus- picious. The lesion was classified as probably benign when all three methods of clinical evaluation classified the lesion as probably benign. Any other combination resulted in the lesion being classified as indeterminate. The fine needle as- piration results were then classified as negative for cancer, suspicious for cancer, or positive for cancer. In order to evaluate the reliability of the fine needle aspiration biopsy, the final pathology reports from tissue obtained from open biopsy, lumpectomy, or mastectomy were compared. Where pathology reports were not available because tissue biopsy was not done, final analysis of the palpable mass was based on follow-up physical as well as radiologic examinations. Exclusions included patients who did not have a combi- nation of physical examination, radiologic study, or fine needle aspiration. We also excluded patients with cysts as well as patients in whom no definable mass both on physical examination and image evaluation could be detected.

The cost savings is calculated as that resulting from avoid- ance of a confirmatory open biopsy and is calculated for average charges for outpatient biopsy including surgeon’s

694 0 1997 by Excerpta Medica, Inc. 0002-961 O/97/$1 7.00

All rights reserved. PII SOOO2-9610(97)00192-X

(FNA FOR SOLID BREAST LESlONS/RUBlN ET AL

TABLE I Clinical Impression Versus Fine Needle Aspiration and Surgical Pathology

Fine Needle Aspiration Surgical Pathology

Clinical Impression Positive Suspicious Negative Positive Negative

Highly suspicious-31 23 (74%) 4 (13%) 4 (13%)f 31 (100%) 0 Indeterminate-20 5 (25%)* 1 (5%) 14 (70%)5 6 (30%) 9 (45%) Benign-34 0 0 34 (100%) 0 9 (26%)

’ One lactating and 7 pregnant patient. + Four false-negative results. * One false-positive in lactating patient. § One false-negative result.

No Biopsy

Follow-up Only

0 5 (25%)

25 (74%)

fee, biopsy suite charges, and histologic evaluation com- pared with charges for technical and interpretation of FNA.

RESULTS A total of 85 charts were reviewed from September 1992

to May 1996 and were categorized as follows: 34 clinically benign, 20 indeterminate for cancer, and 31 highly suspi- cious for cancer. Thirty-seven of the 85 patients (44%) had cancer. In the 34 patients who were clinically benign, all 34 (100%) had a negative fine needle aspiration. Of these 34 patients, 9 had excisional biopsies performed that con- firmed the diagnosis of a benign lesion. The other 25 pa- tients never had open biopsy and were followed up clini- cally and radiographically for 6 to 36 months without the development of cancer (Table I).

Twenty patients were considered indeterminate clinically. The FNA results of these showed that 6 patients (30%) had positive or suspicious aspirations while 14 (70%) had neg- ative FNA results. Final surgical pathology showed that 5 out of the 6 women with positive or suspicious fine needle aspiration had cancer. Fifteen of the 20 women underwent open biopsy with 5 followed up clinically. There was 1 false- negative result from fine needle aspiration and 1 false-pos- itive result on fine needle aspiration in this clinically in- determinate group. The 1 patient with the false-positive fine needle aspiration was later shown on excisional biopsy to have a lactating adenoma (Table I).

Of the 3 1 patients classified clinically as highly suspicious for cancer, 27 (87%) had either positive (23) or suspicious (4) fine needle aspiration results. The remaining 4 (13%) had a negative fine needle aspiration. Final pathology re- ports for each of the 31 patients were available, and all showed cancer. Therefore, 4 had false-negative fine needle aspirations (Table I).

Twenty-five (81%) of the 31 patients classified as highly suspicious on clinical grounds and who had positive or sus- picious FNA biopsy were treated with a single stage surgical procedure, avoiding a separate diagnostic open surgical bi- opsy. Six of the 31 patients required an open surgical biopsy prior to definitive surgical procedure because the FNA bi- opsy was inconclusive. Two of these 6 patients were lac- tating.

The overall results show that fine needle aspiration has a positive predictive value of 97%, a negative predictive value of 90%, a sensitivity of 86%, and a specificity of 98% in our retrospective series (Table II). This is consistent with other studies of fine needle aspiration in patients with pal- pable breast tumors. For patients classified clinically as prob-

TABLE II Positive and Negative Predictive Value Overall

Disease

Fine Needle Aspiration Negative Positive Totals

Negative test TN, 47 FN, 5 52 Positive test* FP, 1 TP, 32 33 Totals 48 37 85

* Positive test included positive and suspicious FNA results. FN = false negative; FP = false positive; TN = true negative; Tf = true positive. Sensitivity = TP/(TP f FN) = 32/37 (86%). Specificity = TN/(TN + FP) = 47/ 48 (98%). Negative predictive value = TN/TN + FN) = 47/52 (90%). Positive predictive value = TFYFP + FP) = 3Z33 (97%).

TABLE Ill

Comparison of Fine Needle Aspiration Results with Open Biopsy or Follow-up Results for Lesions Classified as

Highly Suspicious or Probably Benign

Open Biopsy or Follow-up . _ Fine Needle Aspiration Results Benign Malignant Totals

Benign TN, 34 FN, 4 36 Positive or suspicious FP, 0 TP, 27 27 TOTALS 34 31 65

FN = fake negative; FP = false positive; TN = true negative; TP = truepositive. Sensitivity = TP/(TP + FN) = 27/31 (87.7%). Specificity = TN/m i- FP) = 34/34 (700%). Negative predictive value = TN/(TN + FN) = 34/38 (89.4%). Positive predictive value = TP/rP + FPj = 27/27 (100%).

TABLE IV Cost Analysis of Fine Needle Aspiration Versus Open Biopsy

Fine Needle Aspiration Charges* Open Biopsy Charges*

Technical $150 Facility $055 Interpretation $105 Surgeon $500 Total $255 Total $1,355

*Average charges at our institution.

ably benign or highly suspicious, FNA had a 100% positive predictive value, 100% specificity, 87% sensitivity, and an 89% negative predictive value (Table III).

Analysis of procedural charges for fine needle aspiration versus open biopsy revealed the following: FNA charges total $255 versus open biopsy total $1,355 (Table IV). For those patients in which fine needle aspirate provided ac- curate information, therefore avoiding an open surgical bi-

THE AMERICAN JOURNAL OF SURGERY@ VOLUME 174 DECEMBER 1997 695

IA FOR SOLID BREAST LESIONS/RlJBIN ET AL -

opsy, a savings of $1,100 is realized. These charges do not include charges for consultative services or follow-up charges that would be incurred for both of these procedures.

COMMENTS Fine needle aspiration biopsy for solid palpable breast tu-

mors should be the diagnostic procedure of choice for pa- tients who are classified clinically by physical examination, mammography, and/or ultrasound as probably benign or highly suspicious for cancer. By using fine needle aspiration as the initial diagnostic procedure in these patients, it is possible to avoid open biopsy and go directly to definitive therapy.5 Replacing an open surgical biopsy with a fine nee- dle aspiration prior to definitive surgical therapy has many advantages: (I) It allows for the discussion of surgical op- tions for the treatment of breast cancer and therefore a planned one-stage surgical therapy as occurred in 25 of our 31 patients classified clinically as highly suspicious for can- cer. (2) One can avoid an open excisional biopsy in those patients classified clinically as probably benign when the patient and physician feel comfortable observing the lesion, as resulted in 25 of the 34 lesions in our series. (3) Avoiding an open surgical biopsy saves the patient the trauma of the operating room experience. (4) It results in a cost savings of $1,100 when compared with open surgical biopsy. For patients who are classified clinically as probably benign or highly suspicious, FNA was a reliable first diagnostic step with a positive predictive value of lOO%, specificity of 100%, sensitivity of 87%, and negative predictive value of 89% (Table III). However, it should be emphasized that for lesions classified as highly suspicious, a negative fine needle aspirate as occurred in 4 of our patients (false negative rate of 13%) should not justify these lesions being followed up conservatively. All lesions classified as clinically highly sus- picious need to be resolved ultimately with excisional bi+ opsy in those cases in which INA is either suspicious or negative (Table III).

Our analysis, as well as that of others,6’7 indicate that ob- servation is safe for patients where the physical examina- tion, mammography and/or ultrasound, and fine needle as- piration are benign. The decision to avoid an open surgical biopsy when the fine needle aspirate confirms a benign le- sion should be made prior to performing the RNA. If the patient or clinician feels that regardless of the FNA results they will want the lesion removed anyway, then an FNA should be avoided. However, for those patients and physi- cians who feel comfortable following up a clinically benign lesion when the RNA confirms this, then an open surgical biopsy can be avoided, as occurred in 25 of our 34 patients in this subgroup. In cases in which fine needle aspirate re- sults will not eliminate a surgical biopsy because of either patient or physician concerns, then an FNA should be avoided as this only adds cost to the evaluation of these lesions. Thirty-four of our patients were followed up from 6 to 36 months with a mean of 29 months, and none have developed cancer. Despite our findings, there is still under- standably a certain percentage of patients with palpable breast masses who would prefer to have their lesions re- moved.

For patients classified as indeterminate, fine needle aspi- ration results are not reliable enough to recommend defin-

itive treatment. This is based on the fact we had one false- negative patient in the indeterminate group as well as one lactating patient who had a false-positive fine needle aspi- rate. In these situations it would be reasonable to do either a confirmatory open biopsy in a two-stage procedure or to counsel the patient on the possibility of doing a one-stage procedure with diagnostic biopsy prior to definitive therapy. In addition, 75% (15 of 20) of our patients in this clinically indeterminate group required an open surgical procedure, raising the question of F’NA’s usefulness for these patients. FNA for this moun of oatients should be avoided. as it was both unreliable and did not avoid the need for open surgical biopsy.

In pregnant or lactating women, fine needle aspiration should not be used. In our analvsis, we had 1 pregnant and 2 lactating patients. Two were’shown to have highly sus- picious tumors clinically, and both had suspicious fine nee- dle asoiration bionsies. These 2 patients underwent an open biopsy prior to definitive surgical therapy. Both patients were shown to have cancer. One patient had a false-positive fine needle asniration that was later shown to be a lactating adenoma on excisional biopsy. Cytological changes that oc- cur during pregnancy and lactation results in FNAs that are unreliable in evaluating a breast lesion. Therefore, FNA is of no benefit in these patients and should not be done.

CONCLUSION Patients with solid nalnable breast tumors should be eval-

uated by physical examination, mammography and/or ul- trasound, and fine needle biopsy. Our results indicate the FNA is highlv reliable in patients who are most likely be-

Y I

nign and in those who are most likely malignant. Open surgical biopsy in these patients can be avoided in most circumstances with a cost savings of $1,100 per case. Cy- tological changes that occur during pregnancy and lactation make FNA evaluation inadequate, as occurred in all 3 of our patients, and should be avoided in this subset.

REFERENCES 1. Hermansen C. Paulsen HS, lensen 1, et al. Diagnostic reliability of combined physical exam, mammography and hne needle punc- ture (“triple test”) in breast tumors: a prospective study. Cancer. 1987;60:1866-1871. 2. Hindle W, Payne P, Pan E. The use of fine needle aspiration in the evaluation of persistent palpable dominant breast masses. Am J O&et Gynecol. 1993;168:1814-1819. 3. Costa M, Tadros T, Hilton G, et al. Breast fine needle aspiration cytology. Utility as a screening tool for clinically palpable lesions. Acm Cytol. 1993;37:461-471. 4. Kaufman Z, Shpitz B, Shapiro M, et al. Triple approach in the diagnosis of dominant breast masses: combined physical examina- tion, mammography and fine needle aspiration. .J Surg Oncol. 1994;56:254-257. 5. Gelabert HA, Hsiu JG, Mullen JT, et al. Prospective evaluation of the role of fine needle aspiration biopsy in the diagnosis and management of patients with palpable solid breast lesions. Am Surg. 1990;56:263-267. 6. Vetto J, Pommier R, Schmidt W, et al. Use of the “triple test” for palpable breast lesions yields high diagnostic accuracy and cost savings. Am J Surg. 1995;169:519-522. 7. Sommers RG, Sandier GL, Kaplan MJ, et al. Palpable abnor- malities of the breast not requiring excisional biopsy. Surg Gynec01 Obstet. 1992;125:325-328.

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DISCUSSION S. Michael Roe, MD (Chattanooga, Tennessee): Fine

needle aspiration for cytology in the management of breast disease was introduced in the 193Os, fell into disfavor largely because of concerns of accuracy, was reintroduced 25 to 30 years ago, and has enjoyed varied support since, which has largely been institution dependent.

Our institutional experience has been that an FNA pos- itive for malignancy in a clinically suspicious palpable breast mass is adequate for entering a discussion of malig- nancy and definitive treatment options with the patient. The small degree of residual uncertainty that remains man- dates for most surgeons histological confirmation prior to engaging in definitive therapy. As the authors have shown, that confirmation and definitive treatment can occur at one operative setting. Do you always perform confirmatory bi- opsy with frozen section in this instance?

I am uncertain as to the conclusions of the authors re- garding the role of FNA in clinically indeterminate lesions. If FNA is not performed in pregnant or lactating patients or in a setting of inflamation, false-positive results should be avoided. FNA diagnosed or suggested malignancy in 5 of the 6 patients with confirmed malignancy in this subset. It appears that the procedure was helpful in this group if positive, and if appropriate selection was utilized.

I am uneasy with the reliability of FNA in altering patient management if a palpable solid breast lesion is clinically probably benign. Most patients I see want these lesions re- moved, period. Considerable anxiety has been generated before I see the patient that reassurance or cytologic diag- nosis will not fully alleviate. Most of these lesions are small and the 1% to 2% that will be malignant are likely to be excised with negative margins at a higher percentage than larger lesions taken to surgery without a preoperative di- agnosis. I am concerned that the possibility of a falsely re- assuring, benign diagnosis from FNA in these patients is heightening in comparison to larger lesions, and late diag nosis may occur if the mass is not excised or at least his- tologic confirmation of benign status obtained. Larger sam- ple size will likely reveal this scenario, quite uncomfortable for both patient and surgeon.

Lastly, the cost savings analysis assumes an operative pro- cedure is avoided in benign lesions and the second proce- dure is always avoided in malignant lesions. I suspect the reality is somewhere in between.

F. Charles Brunicardi, MD (Houston, Texas): I am con- cerned about the comment that FNA is a highly reliable tool for diagnosing cancer when your study showed that your false-negative rate is 13%. Would you please clarify that comment for us?

Barry Feig, MD (Houston, Texas): We have used FNA in our institution for a long time. However, I am concerned about the 29 patients that were categorized as being able to have one surgical procedure. Our problem is that our cy- topathologists cannot tell us on FNA whether a lesion is invasive or noninvasive. So, when you take someone to the operating room, you do not know (based on FNA) if they need the lymph nodes dissected or not.

Are the authors defining the surgical procedure as only the breast portion of the procedure and the lymph node dissection as another procedure? Are they determining in- vasion at the time of surgery by frozen section, which itself

is very expensive? If you went to only core biopsy and did not do FNA, then you would avoid the need for frozen section and have a determination of invasion. I would be curious as to how the authors treat that portion of the pro- cedure .

Richard Ftazee, MD (Temple, Texas): I echo Dr. Page’s concerns. Not only is there a problem with false negatives, but the big concern is the false positive and performing a mastectomy that ends up having benign disease. I wonder if the authors could address that.

You also made the comment that FNA is better tolerated and causes less pain than core needle biopsy. Did you have any comparisons of postprocedure pain or any basis for this conclusion?

Jeffrey Levine, MD (St. Louis, Missouri): First, I would like to echo what Dr. Roe said. I find very few patients who want to go home still having a mass in their breast. I know you made the comment briefly in your discussion of the paper that anybody who wanted to have their lesion excised was excluded from this study. I was curious as to what num- ber of patients that amounted to, in comparison with the patients who decided that they were comfortable with an FNA alone.

Second, how did you determine that the FNA was, in fact, a false negative? Did any of these patients delay treatment, resulting in a more advanced stage of cancer, before they underwent definitive surgical therapy?

Kristin Skinner, MD (Los Angeles, California): My big- gest concern is the clinical follow-up of patients with in- determinate lesions. You said you had, I think, 5 patients who fell into that group. You did not tell us what the out- come in those patients were. Did any of those patients go on to develop cancer!

James Edney, MD (Omaha, Nebraska): In your presen- tation, you reported one false-positive FNA. What was the outcome in this case? Did this woman have a mastectomy as a result of this error? Also, you reported four negatives in your highly suspicious group. Did these patients go on to definitive biopsy?

Carey Page, MD (San Antonio, Texas): Do you discrim- inate in your acting on the fine needle aspirate between the patients you are going to handle with a segmental mastec- tomy versus those who may require a modified radical?

CLOSING Mark A. Rubin, MD: In performing the confirmatory bi-

opsy, Dr. Roe, all patients in that group who were felt to have consistent and concordant biopsies went on to defin- itive therapy without a frozen section. Any patient who had a disconcordant result went to open surgical biopsy prior to definitive therapy. This may have taken place, and the dis- cussion may have taken place with the patient as to what possibilities may take place at that point.

There were several questions regarding FNA in the clin- ically indeterminate group. In this group, 5 out of the 6 patients did have FNA in which this would have helped us. We also would have had 15 out of the 20 who went on to open surgical biopsy regardless of the FNA result.

Regarding the anxiety of patients with lumps still left in their breasts, we understand this. For any patient who pre- ferred to have this breast lump removed, this was done.

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and that this was a reliable tool in evaluating a palpable breast mass.

I think that many of the concerns raised by discussants con- cerned patients who had palpable breast masses in the benign group. Again, in this situation, if there was a palpable breast mass that we felt-by ultrasound, mammography, physical ex- amination, and fine needle aspiration-to be negative, we could observe these patients if they felt comfortable with that. This has been shown in other studies as well.

In this situation, the cost savings looked at patients in whom we were able to go over the open surgical biopsy and completely go on to definitive surgical therapy. There were patients who would undergo an open surgical biopsy prior to definitive therapy. In our scenario, the patients who had concordant results would go on to definitive therapy.

Dr. Brunicardi asked whether it was a highly reliable tool in that we had a falsenegative rate of 13%. We felt that the reliability was consistent with others in the literature,

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