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STUDY OF HISTOMORPHOLOGY AND IMMUNOHISTOCHEMICAL ANALYSIS IN BREAST NEOPLASM.

BACKGROUND

Carcinoma of the breast is the most common malignant tumour and the most common cause of death from carcinoma in females all over the world.

The important pathological prognostic factors in invasive breast carcinoma include patient's age, tumour size, lymph node metastasis, nuclear grade, histological grade, histological type, hormone receptor status and HER-2/neu. A single parameter with the strongest prognostic significance is hormone receptor status. [3] Intracellular steroid-hormone receptor proteins, primarily oestrogen receptor (ER) and progesterone receptor (PR) have received intensive study, both as indicator of prognosis and as guide to hormone therapy. [4]

The present study was thus aimed to evaluate the prevalence and to understand the role of ER, PR and HER-2 status in choice of treatment for further management in patients of breast carcinoma.

MATERIALS AND METHODS

A hospital-based prospective observational study was conducted at Department of Surgery, MGM Medical College and MY Hospital, Indore. A total of 50 diagnosed carcinoma breast cases coming to our hospital were taken into study after informed consent. Detailed history was taken from patients and a biopsy specimen was taken from all patients. Gross examination pertaining to overall size of the specimen, nipple and areola, tumour size, margin status and nodal status were carefully studied. The tissue was processed for routine histopathological examination and stained with Haematoxylin and eosin. The slides were then stained with ER, PR and HER2/neu antibodies.

Statistical Methods Applied

Data were statistically described in terms of mean ([+ or -]SD), frequencies (number of cases) and percentages when appropriate. Data were tested first for normal distribution by Kolmogorov-Smirnov test. Comparison of quantitative variables between the study groups was done using student's '? test for independent samples if normally distributed. MannWhitney U test was used for non-normally distributed quantitative data. For comparing categorical data, Chi-square test was performed. Exact test was used instead when the expected frequency was less than 5. For qualitative comparison of tables over 2 x 2 dimensions like TNM staging, p-trend value was calculated. A probability value (p value) less than 0.05 was considered statistically significant. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social Sciences, SPSS Inc., Chicago, IL, USA) version 21.

Inclusion Criteria

1. Clinically diagnosed carcinoma breast in females above 30 years of age.

2. Patients who gave written informed consent.

Exclusion Criteria

1. Those who have undergone any chemoreduction treatment.

2. Patients already treated for contralateral breast cancer.

3. Patients not willing to give written consent.

RESULTS

1. Mean age of the study subjects was 54.32 years, while age at menarche and menopause was 13.12 years and 44.61 years respectively.

2. Most common type of carcinoma seen in present study was invasive ductal carcinoma (90%).

3. Out of the total 50 cases 20% and 42% were in stage I and II respectively, while 36% and 2% were in stage III and IV.

4. Prevalence of positive oestrogen receptor, progesterone receptor and HER-2/neu status was seen in 52%, 48% and 24% cases respectively.

5. No association was observed between age at diagnosis and parity with positive hormonal status.

6. A significant association was observed between increasing tumour size and LN status with positive HER2/neu and ER and PR negative status (p < 0.05).

7. Out of 19 cases of stage III/ IV, approx. 31.6% are ER and PR+, while out of 31 cases in stage I/II 64.5% were ER and PR positive (p < 0.01). Similarly, 22.6% cases of stage I/II were HER-2/neu positive as compared to 21.05% of stage III and IV (p-0.27).

DISCUSSION

A hospital-based prospective observational study was conducted at Dept. of Surgery of a tertiary care hospital with the objective of finding the correlation of ER, PR and HER2/neu incidence with other prognostic factors like age, parity, tumour size and lymph node status. A total of 50 operated cases of carcinoma breast who fulfilled the selection criteria and gave voluntary consent to be a part of the study were enrolled in this study. Following observations were made during the study 1. Over half of the study subjects (60%) were between 40 60 years of age, while 12% were below 40 years of age.

2. Mean age of the study subjects was 54.32 years, while age at menarche and menopause was 13.12 years and 44.61 years respectively.

3. Most of the cases were multipara (94%).

4. About three-fourth of the study subjects belonged to postmenopausal, while 16% were pre-menopausal.

5. Family history of carcinoma breast to first-degree relative was given by 18% cases.

6. Both sides were equally involved in the present study. No case of bilateral carcinoma was seen in our study.

7. Most common type of carcinoma seen in the present study was Invasive ductal carcinoma (90%). Other cases were of malignant phyllodes (4%), mucinous carcinoma (4%) and papillary carcinoma (2%).

8. About half of the cases were in T stage 2, while lymph node involvement was seen in 42% cases. Metastasis was observed in 2% cases.

9. Out of the total 50 cases 20% and 42% were in stage I and II respectively, while 36% and 2% were in stage III and IV.

10. Prevalence of positive oestrogen receptor, progesterone receptor and HER-2/neu status was seen in 52%, 48% and 24% cases respectively.

11. No association was observed between age at diagnosis and positive oestrogen receptor, progesterone receptor and HER-2/neu status (p > 0.05).

12. No association was observed between parity and positive oestrogen receptor, progesterone receptor and HER2/neu status (p > 0.05).

13. A significant association was observed between increasing tumour size with positive HER-2/neu positive status and ER and PR negative status (p < 0.05).

14. Out of 29 cases with negative lymph node status, positive oestrogen and progesterone receptor status was seen in 19 (65.5%) and 17 (58.6%), while out of 21 cases with positive LN status 66.7% each were ER and PR negative (p < 0.05). Similarly, out of the 29 cases with negative lymph node status 86.2% were HER-2/neu negative and out of 21 positive cases, 38.1% were HER-2/neu positive (p < 0.05).

15. Out of the 19 cases of stage III/ IV approx. 31.6% are ER and PR+, while out of 31 cases in stage I/II 64.5% were ER and PR positive (p < 0.01). Similarly, 22.6% cases of stage I/II were HER-2/neu positive as compared to 21.05% of stage III and IV (p-0.27).

CONCLUSION

The frequency of carcinoma of breast is high in postmenopausal group. The most common tumour pathology found in the study was Ductal Carcinoma. Definitive prognostic correlation was found with ER and PR receptors.

HER-2/neu expression was high in advanced diseases like axillary node positive patients. [5,6] The clinical importance of these prognostic markers in the management of breast cancer in clinical practice is strongly recommended.

REFERENCES

[1] Midulla C, Cenci M, De lorio P, et al. The value of fine needle aspiration cytology in the diagnosis of breast proliferative lesions. Anticancer Research 1995;15(6B):2619-22.

[2] Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer Journal for Clinicians 2011;61(2):69-90.

[3] Lin CH, Lien HC, Hu FC, et al. Fractionated evaluation of immunohistochemical hormone receptor expression enhances prognostic prediction in breast cancer patients treated with tamoxifen as adjuvant therapy. J Zhejiang Univ Sci B 2010;11(1):1-9.

[4] Donegan WL. Tumor-related prognostic factors for breast cancer: CA Cancer Journal for Clinicians 1997;47(1):28-51.

[5] Mustafa IA, Bland KI. Physiologic effects of steroid hormones and postmenopausal hormone replacement on the female breast and breast cancer risk. Annals of Surgery 1998;228(5):638-51.

[6] Osborne CK. Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat 1998;51(3):227-38.

Manish Kaushal (1), ArvindShukla (2), Pankaj Patil (3)

(1) Associate Professor, Department of Surgery, MGMMC and MY Hospital, Indore, Madhya Pradesh.

(2) Assistant Professor, Department of Surgery, MGMMC and MY Hospital, Indore, Madhya Pradesh.

(3) Junior Resident, Department of Surgery, MGMMC and MY Hospital, Indore, Madhya Pradesh.

'Financial or Other Competing Interest': None.

Submission 11-10-2017, Peer Review 05-02-2018, Acceptance 12-02-2018, Published 19-02-2018.

Corresponding Author:

Dr. Arvind Shukla, #335, BC, Scheme 140, Pipliyahana, Indore-452016. E-mail: drshuklaarvind@gmail.com

DOI: 10.14260/jemds/2018/238
Table 1. Association of Hormonal Receptors with Age a
Presentation

Age at Diagnosis (Yrs.)

Variables   Results    N    Mean     SD     P-value

ER          Negative   24   53.58   10.23    0.54
            Positive   26   54.90   11.57
PR          Negative   26   54.68   11.93    0.69
            Positive   24   53.81   9.75
HER-2/Neu   Negative   38   54.91   11.58     0.3
            Positive   12   52.25   8.35

No association was observed between age at diagnosis ant
positive oestrogen receptor, progesterone receptor and HER
2/neu status (p > 0.05).

Table 2. Association of Hormonal Receptors with
Age at Menarche

Age at Menarche (Yrs.)

Variables   Results    N    Mean     SD    P-value

ER          Negative   24   13.43   3.23    0.79
            Positive   26   13.01   3.10
PR          Negative   26   12.96   2.39    0.61
            Positive   24   13.38   3.65
HER-2/Neu   Negative   38   13.21   3.54    0.48
            Positive   12   12.49   2.44

No association was observed between age at menarche
and positive oestrogen receptor, progesterone receptor and
HER-2/neu status (p > 0.05).

Table 3. Association of Hormonal Receptors with Age at
Menopause

Age at Menopause (Yrs.)

Variables   Results    N    Mean     SD    P-value

ER          Negative   24   44.58   5.18    0.891
            Positive   26   44.79   5.56
PR          Negative   26   44.12   5.09    0.67
            Positive   24   44.91   5.77
HER-2/Neu   Negative   38   44.77   5.91    0.59
            Positive   12   43.81   5.32

No association was observed between age of menopause
and positive oestrogen receptor, progesterone receptor and
HER-2/neu status (p > 0.05).

Table 4. Association of Hormonal Receptors with Parity

Parity         ER              PR               HER-2/NEU

          Nega-   Posi-   Nega-   Posi-   Nega-    Posi-
          tive    tive    tive    tive     tive    tive

Multi      22      25      24      23       35      12
          46.8%   53.2%   51.1%   48.9%   74.5%    25.5%
Primi       2       1       2       1       3        0
          66.7%   33.3%   66.7%   33.3%   100.0%   0.0%
Total      24      26      26      24       38      12
P-value       0.345           0.489            0.664

No association was observed between parity and positive
oestrogen receptor, progesterone receptor and HER-2/neu
status (p > 0.05) and HER-2/neu status (p > 0.05).

Table 5. Association of Hormonal Receptors with Tumour Size

Tumour            ER               PR               HER-2/Neu
Size (TNM)

             Nega-   Posi-    Nega-   Posi-   Nega-    Posi-
             tive     tive    tive    tive     tive    tive

0              0       3        1       2       3        0
             0.0%    100.0%   33.3%   66.7%   100.0%   0.0%
1              2       5        2       5       7        0
             28.6%   71.4%    28.6%   71.4%   100.0%   0.0%
2             11       15      12      14       22       4
             42.3%   57.7%    46.2%   53.8%   84.6%    15.4%
3              3       1        3       1       2        2
             75.0%   25.0%    75.0%   25.0%   50.0%    50.0%
4              8       2        8       2       4        6
             80.0%   20.0%    80.0%   20.0%   40.0%    60.0%
Total         24       26      26      24       38      11
P-value      <0.05            <0.05           <0.05

A significant association was observed between increasing
tumour size with positive HER-2/neu positive status and ER
and PR negative status (p < 0.05).

Table 6. Association of Hormonal Receptors with Lymph
Node Involvement

Lymph           ER               PR              HER-2/Neu
Node
Status

           Nega-   Posi-    Nega-   Posi-   Nega-   Posi-
           tive     tive    tive    tive    tive    tive

Negative    10       19      12      17      25       4
           34.5%   65.5 %   41.4%   58.6%   86.2%   13.8%
Positive    14       7       14       7      13       8
           66.7%   33.3 %   66.7%   33.3%   61.9%   38.1%
Total       24       26      26      24      38      12
P-value    <0.01            <0.05           <0.05

Out of 29 cases with negative lymph node status, positive
oestrogen and progesterone receptor status was seen in 19
(65.5%) and 17 (58.6%), while out of 21 cases with positive
LN status (66.7%) each were ER and PR negative (p < 0.05).
Similarly, out of 29 cases with negative lymph node status,
86.2% were HER-2/neu negative and out of 21 positive cases
38.1% were HER-2/neu positive (p < 0.05).

Table 7. Association of Hormonal Receptors with TNM Staging

TNM             ER               PR              HER-2/Neu

Stage     Nega-    Posi-   Nega-    Posi-   Nega-   Posi-
           tive    tive     tive    tive    tive     tive

I           6        4       7        3       8       2
          60.0%    40.0%   70.0%    30.0%   80.0%   20.0%
II          5       16       6       15      16       5
          23.8%    76.2%   28.6%    71.4%   76.2%   23.8%
III         12       6       12       6      15       3
          66.7%    33.3%   66.7%    33.3%   83.3%   16.7%
IV          1        0       1        0       0       1
          100.0%   0.0%    100.0%   0.0%    0.0%    100.0%
Total       24      26       26      24      39       11
P-value   <0.01            <0.01            0.27

Out of the 19 cases of stage III/IV approx. 31.6% are ER and
PR+, while out of 31 cases in stage I/II 64.5% were ER and PR
positive (p < 0.01).
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Title Annotation:Original Research Article
Author:Kaushal, Manish; Shukla, Arvind; Patil, Pankaj
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Report
Date:Feb 19, 2018
Words:2246
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