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Can features evaluated in the routine pathologic assessment of lymph node-negative estrogen receptor--positive stage I or II invasive breast cancer be used to predict the oncotype DX recurrence score?

Improved breast imaging, combined with increasing public awareness, has resulted in a rise in the rate of early stage breast cancer detection. (1) One challenge for the oncologist in these cases is to administer chemotherapies when beneficial but not to overtreat. Specifically, for patients with lymph node-negative, estrogen receptor-positive invasive breast cancer, up to 80% will be disease free at 15 years when treated by surgery and tamoxifen alone. (2) However, findings from the National Surgical Adjuvant Breast and Bowel Project-20 trial have demonstrated that adding chemotherapy to tamoxifen and surgery results in improved overall survival and recurrence-free survival in this patient population. (3) This benefit is small, and so many patients are subject to unnecessary chemotherapy treatment.

Oncotype DX (Genomic Health Inc, Redwood City, California) is a commercially available multigene reverse transcription-polymerase chain reaction (RT-PCR) assay that is used to quantify the risk of distant recurrence in patients with stage I or II hormone receptor-positive, lymph node-negative invasive breast cancer who will be treated with tamoxifen. (4) Results are reported as a numerical Recurrence Score. The Recurrence Scores are divided into low- (0-17), intermediate- (18-30), and high-risk (>30) groups, with a group average risk of distant recurrence of 6.8%, 14.3%, and 30.5%, respectively. Additionally, patients with a high Recurrence Score derive a large benefit from chemotherapy, while those with a low Recurrence Score derive little if any benefit from chemotherapy. For patients with an intermediate Recurrence Score, the benefit of chemotherapy is uncertain. (5) Recently, the American Society of Clinical Oncology (ASCO) offered a specific recommendation for the utilization of the Oncotype DX assay to identify those patients with lymph node-negative, estrogen receptor-positive cancer and low Recurrence Score who might not require chemotherapy. (6)

The Oncotype DX assay gene panel consists of 16 cancer genes and 5 reference genes. The cancer genes measured include a proliferation set (5 genes), hormone receptor set (5 genes), HER2 amplicon set (2 genes), invasion set (2 genes), a marker for inflammatory cells (CD68), and a gene for GSTM-1. (4) In the routine pathology assessment of all invasive breast cancers, hormone receptors (via immunohistochemistry), HER2/neu (via immunohistochemistry and/or fluorescence in situ hybridization analysis), and proliferation rates (via a mitotic count score) are evaluated. Therefore, at least 12 of the 16 gene markers evaluated in the Oncotype DX assay are in part addressed by routine pathologic assessment. In this study we reviewed the pathology data of 138 breast cancer cases for which an Oncotype DX assay was performed on the tumors. We sought to determine if hormone receptor evaluation, HER2/neu assessment, mitotic count score, or any other factors that are part of the routine pathologic evaluation of all breast cancers could predict Oncotype DX assay Recurrence Score results in these cases.

MATERIALS AND METHODS

One hundred and thirty-eight cases of invasive breast cancer from 135 patients were identified for which both results of an Oncotype DX assay and pathology data of the invasive cancer were available for review. All cases were retrieved from the files of the Department of Pathology of the Montefiore Medical Center Laboratories, Bronx, New York. In all cases the invasive breast cancer was stage I or II, estrogen receptor positive, and lymph node negative.

In 133 cases the slide from the block sent for Oncotype DX analysis was reviewed by 1 pathologist and a nuclear grade, tubule score, and mitotic count score were determined with the Nottingham grading system. (7) In 5 cases the slides were not available for review. Additional information obtained from the patient's report included tumor size, patient age, laterality, estrogen receptor result, progesterone receptor (PR) result, and HER2/neu result. Both estrogen and progesterone receptor immunostains were performed with the DakoCytomation EnVision+ System (Dako, Carpinteria, California). The anti-estrogen receptor antibody used was clone1D5 (Dako) in a dilution of 1:50 and the anti-PR antibody used was clone 636 (Dako) in a dilution of 1:200. A cutoff level of 10% positive nuclear staining of any intensity was used to determine a positive estrogen and/or progesterone receptor result. In all cases with both a negative PR result and a low Recurrence Score, the PR immunostained slides were reviewed and the level of PR staining was quantified. HER2/neu was determined via immunohistochemistry with the HercepTest (Dako) as per manufacturer's guidelines. When the HercepTest yielded a borderline result of 2+, a fluorescence in situ hybridization test was done with Vysis probes (Abbott Molecular, Des Plaines, Illinois) as per manufacturer's guidelines. Recurrence Scores were classified as low if less than 18, intermediate if between 18 and 30, and high if greater than 30, as per Oncotype DX assay guidelines.

This study was approved by the institutional review board of the Montefiore Medical Center, Bronx, New York.

Statistical Analysis

Correlations between Recurrence Score with continuous and ordinal variables were estimated with the Spearman rank correlation coefficient. The Fisher exact test was used to evaluate the association between categorical variables. The logistic regression model was also fit to the data to identify independent predictors of low Recurrence Score (<18).

RESULTS

The patients consisted of 135 women with lymph node-negative, hormone receptor-positive, stage I or II invasive breast cancer. Three patients had 2 tumors each. The patients ranged in age from 27 to 86 years, with a mean age of 58 years and a median age of 59 years. Eighty-one cases (59%) had a low Recurrence Score, 44 cases (32%) had an intermediate Recurrence Score, and 13 cases (9%) had a high Recurrence Score, as per Oncotype DX assay guidelines.

Four patients had a tumor size greater than 3 cm, and 3 had a high Recurrence Score. One patient with a 3.5-cm tumor had a Recurrence Score of 5; however, the tumor was a mucinous carcinoma arising from an intracystic papillary cancer. For the remaining patients, the tumor size ranged from 3 cm to 0.4 cm. The relationship between tumor size and Recurrence Score is shown in Table 1. The correlation between tumor size and Recurrence Score was modest but statistically significant (Spearman rank correlation coefficient, 0.18; P = .04).

In all cases, the tumors were estrogen receptor positive. In 106 cases the tumors were progesterone receptor positive and the Recurrence Scores in these cases ranged from 1 to 39, with a mean Recurrence Score of 14. In 32 cases the tumors were progesterone receptor negative (<10% positive nuclear staining) and the Recurrence Scores in 31 of 32 cases ranged form 12 to 50, with a mean Recurrence Score of 28. In 1 progesterone receptor-negative tumor, the Recurrence Score was 5; however, this was a case of a mucinous carcinoma arising in an intracystic papillary cancer. There were only 5 progesterone receptor-negative cases with a low Recurrence Score, and the characteristics of these tumors, including percentage of progesterone receptor-positive staining cells, is provided in Table 2. The association between progesterone receptor and Recurrence Score was highly significant, as shown in Table 3 (P < .001).

The mitotic count score was 3 in 16 cases. In all of these cases, the Recurrence Score was 16 or higher. Recurrence Score, as it relates to mitotic count score, is illustrated in Table 3; the association was highly significant (P < .001). In 6 cases, the tumor was both progesterone receptor negative and exhibited a mitotic count score of 3, and in all these cases the Recurrence Score was high. In the remaining 7 cases with a high Recurrence Score, the tumor showed either a mitotic count score of 3 or was progesterone receptor negative. In all 12 cases with both a negative progesterone receptor result and a mitotic count score greater than 1, the Recurrence Score was either intermediate or high. Recurrence Score, as it relates to combined progesterone receptor result and mitotic count score, is illustrated in Table 4.

In 5 cases the nuclear grade was 1 and the Recurrence Scores in these cases ranged from 14 to 28, with a mean Recurrence Score of 19. In 94 cases the nuclear grade was 2 and the Recurrence Scores in these cases ranged from 1 to 50, with a mean Recurrence Score of 16. In 34 cases, the nuclear grade was 3 and the Recurrence Scores in these cases ranged from 6 to 50, with a mean Recurrence Score of 24. The relationship between Recurrence Score and nuclear grade is illustrated in Table 3 and was statistically significant (P < .001).

In 20 cases the tubule score was 1 and the Recurrence Scores in these cases ranged from 8 to 25, with a mean Recurrence Score of 14. In 38 cases the tubule score was 2 and the Recurrence Scores ranged from 3 to 36, with a mean Recurrence Score of 15. In 75 cases the tubule score was 3 and the Recurrence Scores in these cases ranged from 1 to 50, with a mean Recurrence Score of 19. The relationship between Recurrence Score and tubule score is illustrated in Table 3 and was not statistically significant (P = .06).

In 49 cases the Nottingham grade was 1 and the Recurrence Scores in these cases ranged from 4 to 28, with a mean Recurrence Score of 15. In 63 cases the Nottingham grade was 2 and the Recurrence Scores in these cases ranged from 1 to 50, with a mean Recurrence Score of 15. In 21 cases the Nottingham grade was 3 and the Recurrence Scores in these cases ranged from 15 to 50, with a mean Recurrence Score of 30. The relationship between Nottingham grade and Recurrence Score is illustrated in Table 3 and was statistically significant (P < .001).

HER2/neu results were positive in only 3 cases, and the Recurrence Scores were 11 (low) in 2 cases and 19 (intermediate) in 1 case.

A logistic regression model with a stepwise approach was also fit to the data to identify independent predictors of low Recurrence Score (<18). The final multivariable logistic model included PR status (P < .001) and mitotic count score (P < .001) only as significant predictors of low Recurrence Score. The adjusted odds ratio for a low Recurrence Score comparing progesterone receptor-positive to progesterone receptor-negative cancer was 17.5 (95% confidence interval [CI], 5.3-58.0). In addition, the adjusted odds ratio for a low-risk score per unit decrease in mitotic count score was 4.2 (95% CI, 2.1-8.5). The positive predictive value for an intermediate or high Recurrence Score, for a subject with progesterone receptor-negative results and mitotic count score greater than 1, was 12/12 or 100% (95% CI, 74%-100%).

COMMENT

Oncotype DX is a commercially available multigene RT-PCR assay that is used to quantify the risk of distant recurrence in patients with stage I or II, hormone receptor-positive, lymph node-negative invasive breast cancer who will be treated with tamoxifen. (4) Results are reported as a numerical Recurrence Score. The ASCO guidelines offer a specific recommendation for the use of this assay to help determine which of these groups of patients with breast cancer would have a low Recurrence Score and who then might avoid chemotherapy. (6) The cost of this assay is approximately $3800; yet, the activity of 12 of 16 component genes measured are assessed, at least in part, in the routine pathologic evaluation of all breast cancers. In our study we sought to determine if any of the components evaluated in the routine pathologic assessment of all breast cancers could be used to predict Recurrence Score. We found that in all cases with both a negative progesterone receptor result, as determined via immunohistochemistry, and a mitotic count score of 3 with Nottingham grading system, (7) the Recurrence Score was high. We propose that these results, as determined during routine pathologic examination, could serve as a surrogate marker for a high Recurrence Score.

One recent study (8) demonstrated that the hormone receptor gene group, HER2/neu gene group, and the proliferation gene group have the largest coefficient of all gene groups used in calculation of the Recurrence Score. In our study none of the 12 cases with both a negative progesterone receptor result, as determined by immunohistochemistry, and a mitotic count score greater than 1 had a low Recurrence Score; thus, our results support the importance of the proliferation gene group and hormone receptor gene group in the determination of the Recurrence Score. In our study we identified only 3 HER2/neupositive cancers, and the Recurrence Scores were low in 2 cases and intermediate in 1. Other studies (9,10) report that positive HER2/neu expression is significantly associated with a high Recurrence Score. However, even in these studies a few cases of HER2/neu-positive cancers were found to have a low Recurrence Score. Flanagan and colleagues (10) reported that 4 of 7 HER2/ neu-positive cases had either a low or intermediate Recurrence Score and a study by Wolf and colleagues (9) reported 2 HER2/neupositive cancers with low Recurrence Score. Of note, the 3 HER2/neu-positive cases in our study all expressed very high levels of both estrogen and progesterone receptors and showed a mitotic count score of 1. Since HER2/neupositive cancers generally are not sent for Oncotype testing, we cannot comment on the significance of this finding in only 3 cases.

In a study by Kamal et al, (11) 6 academic oncologists reviewed 31 cases of lymph node-negative, estrogen receptor-positive invasive breast cancer to determine if they could predict Oncotype DX Recurrence Score by using standard prognostic criteria. They concluded that they could identify most patients with a high Recurrence Score, but standard prognostic criteria poorly discriminated between low and intermediate risk scores. Our observations support their conclusions. In our study there were no patients with both a positive progesterone receptor result and a mitotic count score less than 3 who had a high Recurrence Score, and all patients with both a negative progesterone receptor result and mitotic count score of 3 had a high Recurrence Score. Of the 70 cases with both a positive progesterone receptor result and mitotic count score of 1, the Recurrence Score was intermediate in 14 cases and low in 54 cases, and we were unable to discriminate between them on the basis of our pathologic examination. We suspect that the other genes tested by Oncotype, and not routinely considered in pathologic examination, such as CD68 and the invasion group genes, might account for the 14 cases of progesterone-positive, low mitotic-count-score cases with an intermediate Recurrence Score. Immunohistochemical evaluation for CD68 or the invasion group genes evaluated by Oncotype might be of interest in these cases.

The Oncotype DX assay specifically predicts breast cancer recurrence in patients who will receive tamoxifen.4 It is well established that absence of progesterone receptor in estrogen receptor-positive invasive breast cancer is associated with tamoxifen resistance. (12) When estrogen receptor-positive breast cancer is divided into progesterone receptor negative and positive, there is a greater than 2 1/2-fold difference in hormone responsivity in favor of those containing both receptors. Progesterone receptor is an estrogen-inducible protein. Progesterone receptor expression is considered a marker of the integrity of the estrogen metabolic pathway and hence a functional hormone response system. (13,14) Thus, our findings that only 5 of 29 patients with absence of progesterone receptor had a low Recurrence Score is not unexpected. The Recurrence Score distribution in these 5 cases included 1 patient with a Recurrence Score of 16, 3 patients with a Recurrence Score of 15, and 1 patient with a mucinous carcinoma arising in association with an intracystic papillary carcinoma and a Recurrence Score of 5. Although the Oncotype test guidelines consider all Recurrence Scores below 18 to be low, a Recurrence Score of 11 has been shown to be associated with a risk of relapse of about 10%, which is a threshold often used clinically to recommend adjuvant chemotherapy in addition to hormone therapy. Additionally, a trend that favors adding chemotherapy becomes apparent at a Recurrence Score of 11. (15) A new clinical trial, the Trial Assigning Individualized Option for Treatment (TAILORx), (15) will attempt to better define whether there is a benefit from chemotherapy for patients with an intermediate Recurrence Score. In this trial the Recurrence Score ranges are redefined as low when less than 11; intermediate, 11-25; and high, greater than 25. With these new ranges, only 1 of 19 or 3% of patients with a negative progesterone receptor result, as determined by immunohistochemistry, would have a low Recurrence Score.

Baehner et al (16) reported on recurrence-free interval in 776 patients enrolled in the Eastern Cooperative Oncology Group breast cancer study E2197. They specifically studied the relationship between tumor-grade components by using Nottingham criteria and relapse-free interval. They found that for patients with hormone receptor-positive breast cancer with 0 to 3 positive nodes and treated with both chemotherapy and hormone therapy, high mitotic figures (>20) were associated with recurrence. Additionally, they found that nuclear grade and tubule formation had little association with recurrence. Similarly, we found an association between elevated Recurrence Score and high mitotic count score. All 16 patients with a mitotic count score of 3 had a Recurrence Score of 16 or higher. Nineteen of 21 patients with a mitotic count score of 2 had a Recurrence Score greater than 10. By applying the new cutoff range of less than 11 for a low Recurrence Score, as detailed in the TAILORx trial, (15) 100% of patients with a mitotic count score of 3 and 90% of patients with a mitotic count score of 2 would have an intermediate or high Recurrence Score. Both Nottingham grade and nuclear grade did show a statistically significant correlation with Recurrence Score in our study (P < .001); however, with the multivariable analysis, the only variables independently associated with an intermediate or high Recurrence Score were negative progesterone receptor result and mitotic count score greater than 1.

Flanagan and colleagues (10) reported on 42 cases of lymph node-negative, estrogen receptor-positive invasive breast cancer and showed that Recurrence Score is significantly correlated with Nottingham grade, estrogen receptor and progesterone receptor immunohistochemical score, and HER2/ neu status. They concluded that the relationship between Nottingham grade and Recurrence Score appears to indicate that it is unnecessary to perform Oncotype DX testing on cases that are Nottingham grade 1 or 3, as the Recurrence Score for the most part correlates with the Nottingham grade. They found no Nottingham grade 3 cases with a low Recurrence Score and no Nottingham grade 1 cases with a high Recurrence Score. In our larger study we found 2 of 21 Nottingham grade 3 cases with a low Recurrence Score. Similar to their findings, we found no Nottingham grade 1 cases with a high Recurrence Score.

In summary, our study suggests that in some cases of lymph node-negative, estrogen receptor-positive invasive breast cancer, information obtained through routine pathologic evaluation can be used to predict the Oncotype DX Recurrence Score results. Specifically, for patients with an invasive breast cancer showing both negative progesterone receptor by immunohistochemistry and a mitotic count score of 3, the Recurrence Score can be predicted to be high, as it was in 100% of our cases. Additionally, in patients with both a mitotic count score of greater than 1 and a negative progesterone receptor result, the Recurrence Score can be predicted to be intermediate or high, as it was in 100% of patients. Additionally, for patients with a mitotic count score of 3 or a negative progesterone receptor result, as determined by immunohistochemistry, the Recurrence Score can be predicted to be intermediate or high, as it was in 95% and 81% of our cases, respectively. If the goal of the oncologist is to omit chemotherapy, which would be supported by a low Recurrence Score, the contribution of Recurrence Score determination in this subset of patients may be low. As our experience with this assay widens, we anticipate larger multi-institutional studies to further evaluate how routine pathology evaluation of breast cancer can be used to predict Oncotype DX assay results. Finally, it remains to be seen if clinical data of recurrence in our patient population support the use of the Oncotype Dx assay more than pathologic and clinical variables.

References

(1.) Norman SA, Localio AR, Zhou L, et al. Benefit of screening mammography in reducing the rate of late-stage breast cancer diagnoses. Cancer Causes Control. 2006;17(7):921-929.

(2.) Fisher B, Jeong JH, Bryant J, et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long term findings from the National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. Lancet. 2004:364(9437):858-868.

(3.) Fisher B, Digman J, Wolmark N, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997;89(22):1673-1682.

(4.) Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. NEJM. 2004;351(27):2817 2826.

(5.) Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-3734.

(6.) Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287-5312.

(7.) Elston CW, Ellis IO. Pathologic 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(5):403-410.

(8.) Watson D, Palmer G, Baker J, et al. The impact of Recurrence Score due to patient variation in the quantitative expression of individual genes or gene groups. 29th Annual San Antonio Breast Cancer Symposium; 2006; San Antonio, TX. Abstract 6039.

(9.) Wolf I, Ben-Baruch N, Frommer R, et al. Association between standard clinical and pathologic characteristics and the 21-gene Recurrence Scorein breast cancer patients. Cancer 2007;112 (4):731-736.

(10.) Flanagan MB, Dabbs DJ, Brufsky AM, Beriwal S, Bhargava R. Histopathologic variables predict Oncotype DX Recurrence Score. Mod Pathol. 2008; 21(10):1255-1261.

(11.) Kamal AH, Loprinzi CL, Reynolds AC, et al. How well do standard prognostic criteria predict oncotype DX scores? In: 2007 ASCO Annual Meeting Proceedings. J Clin Oncol. 2007;25(pt 1)(suppl 18S). Abstract 576.

(12.) Arpiino G, Weiss H, Lee AV, et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst. 2005:97(17):1254-1261.

(13.) Ponzone R, Montemurro F, Maggiorotto F, et al. Clinical outcome of adjuvant endocrine treatment according to PR and Her-2 status in early breast cancer. Ann Oncol. 2006;(17):1631-1636.

(14.) Rakha EA, El-Sayed ME, Green AR, et al. Biologic and clinical characteristics of breast cancer with single hormone receptor-positive phenotype. J Clin Oncol. 2007;25(30):4772-4778.

(15.) Sparano JA. The TAILORx trial: individualized options for treatment. Community Oncol. 2006;3:494-496.

(16.) Baehner Fl, Goldstein LJ, Gray R, et al. Analysis of revised Nottingham grade constituitive components and recurrence free interval in ECOG breast cancer study E2197 [abstract]. 97th Annual Meeting of the USCAP. Mod Pathol. 2008;21.

Jena Auerbach, MD; Mimi Kim, ScD; Susan Fineberg, MD

Accepted for publication February 15, 2010.

From the Department of Pathology, Montefiore Medical Center (Drs Auerbach and Fineberg) and the Albert Einstein College of Medicine (Dr Fineberg), Bronx, New York; and Epidemiology and Population Health, Albert Einstein College of Medicine of Yeshivah University, Bronx, New York (Dr Kim).

The authors have no relevant financial interest in the products or companies described in this article.

Presented in part as an abstract/poster at the annual meeting of the United States and Canadian Academy of Pathology, Boston, Massachusetts, March 7-13, 2009.

Reprints: Susan Fineberg, MD, Department of Pathology, Montefiore Medical Center, 4th Floor Silver Zone, 111 East 210th St, Bronx, NY 10467 (e-mail: sfineber@montefiore.org
Table 1. Relationship Between Tumor Size and
Oncotype DX Recurrence Score (RS) (a,b)

Tumor
size (cm) >3 >2-3 > 1.5-2 >1-1.5 > 0.5-1 [less than or
 equal to] 0.5
No. of
cases 4 19 23 55 32 5

RS range 5-49 6-40 2-36 1-50 5-32 13-50

Mean RS 32 23 15 17 15 27

(a) Spearman correlation coefficient, r = 0.18.

(b) Fisher exact P value = .04.

Table 2. Characteristics of Progesterone Receptor (PR)-Negative
Cases With a Low Recurrence Score (RS)

Case No. PR-Positive PR Intensity RS ER-Positive
 Cells, % Cells, %

1 5 Strong 15 100
2 0 Not applicable 15 95
3 1 Strong 16 70
4 5 Moderate 15 80
5 5 Strong 5 100

Case No. Tumor Type

1 Invasive ductal cancer
2 Invasive ductal cancer
3 Invasive ductal cancer
4 Invasive lobular cancer
5 Mucinous carcinoma/intracystic
 papillary cancer

Abbreviation: ER, estrogen receptor.

Table 3. Bivariate Associations Between Pathologic
Characteristics and Oncotype DX Recurrence Score (RS)

 RS RS RS P
Characteristic [less than 18-30 > 30 Value
 or equal to] 17

PR status, No. (%) <.001
Negative 5 (15.6) 17 (53.3) 10 (31.3)
Positive 76 (71.7) 27 (25.5) 3 (2.8)

Mitotic count score,
No. (%) <.001
1 66 (47) 29 (21.8) 1 (0.8)
2 10 (8) 8 (6) 3 (2.2)
3 1 (0.8) 6 (4.5) 9 (6.8)

Nuclear grade,
No. (%) <.001
1 2 (1.5) 3 (2.3) 0 (0)
2 65 (49) 26 (19.6) 3 (2.3)
3 11 (8.3) 13 (9.8) 10 (7.5)

Tubule score,
No. (%) .06
1 15 (11.3) 5 (15.6) 0 (0)
2 28 (21) 11 (8.3) 1 (0.8)
3 40 (30) 23 (17.3) 12 (9)

Nottingham grade,
No. (%) <.001
1 34 (25.6) 15 (11.3) 0 (0)
2 42 (31.6) 18 (13) 3 (2.3)
3 2 (1.5) 8 (6) 11 (8.3)

Abbreviation: PR, progesterone receptor.

Table 4. Association Between Mitotic Count Score
and Oncotype DX Recurrence Score (RS) Stratified by
Progesterone Receptor Status
 RS RS RS
 [less than or 18-30 > 30 P Value
 equal to] 17
Progesterone receptor Mitotic
count score <.001
1 4 13 1
2 0 3 3
3 0 0 6

Progesterone receptor +
Mitotic count score <.001
1 62 15 0
2 10 5 0
3 1 6 3
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Author:Auerbach, Jena; Kim, Mimi; Fineberg, Susan
Publication:Archives of Pathology & Laboratory Medicine
Date:Nov 1, 2010
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