1. Brief description of cases
Case 1 Female, 55 years old. She was admitted to the hospital on February 23, 2006 due to “intermittent left nipple hematochezia for 20 d”. Examination: bilateral breast symmetry, no swelling. No enlarged lymph nodes were found in both axillae. She had a history of hypertension, type 2 diabetes mellitus, post cesarean section, and post cholecystectomy. Menopausal, no special menstrual or marital history. Denied family history of breast cancer and ovarian cancer.
Ultrasound examination showed localized ductal dilatation in the lateral left nipple, with the widest point reaching 0.5 cm, not excluding intraductal papilloma. Lymph node enlargement was seen in the left axilla. Mammogram did not show any significant abnormality. No tumor cells were found in the smear of the overflow. Lobectomy was performed on the left mammary gland. Frozen pathology showed intraductal carcinoma of the left breast with suspicious interstitial infiltration. One anterior sentinel lymph node biopsy was taken and the frozen pathology showed suspicious metastatic carcinoma. The postoperative pathology showed: ductal carcinoma in situ in the left breast with localized multifocal mesenchymal infiltration of about 2 mm in diameter and metastatic carcinoma in the axillary lymph nodes (8/19). Immunohistochemistry: ER (+), PR (-), C-erbB2 (+), P53 (-), E-cadherin (-), CyclinD1 (-), Ki67 < 5%. Postoperative diagnosis: left breast cancer pT1apN2cM0. Postoperative adjuvant treatment: CA sequential T regimen chemotherapy (CTX 600mg/m2, THP 50mg/m2, 1 time every 21d x 4; sequential polyene paclitaxel 75mg/m2, 1 time every 21d x 4) and ipsilateral axillary adjuvant radiotherapy. Post sequential endocrine therapy (oral letrozole 2.5 mg once daily).
Case 2 Female, 70 years old. She was admitted to the hospital on March 5, 2007, because of “hematochezia in the left breast for 2 weeks”. Examination: no mass in bilateral breast, no enlarged lymph nodes in bilateral axilla. She had a history of hypertension, tuberculosis, postoperative hepatic hemangioma, and bilateral mastectomy for fibroadenoma. She was menopausal and had no special history of menstrual marriage. Family history of breast and ovarian cancer was denied.
Ultrasound examination showed multiple hypoechoic nodules with poorly defined borders in the upper inner quadrant of the left breast near the areola area, with a maximum of 1.0 cm×0.8 cm, suspicious of breast cancer. The mammogram showed a mass in the upper left breast with a high probability of breast cancer. A small number of heavily anisotropic ductal epithelial cells were seen in the smear of the overflow. Fine needle aspiration cytology of the mass showed cancer cells. Modified radical surgery of left breast cancer was performed. Postoperative pathology showed: ductal carcinoma in situ of the breast, tumor size 6 cm×5 cm×0.7 cm; most of the area was ductal carcinoma in situ with necrosis and calcification, pinkish type and lobular carcinoma; a few parts had interstitial microinfiltration, diameter <1 mm, ductal carcinoma, axillary lymph node 0/16 carcinoma metastasis. Immunohistochemistry: ER (++++), PR (-), C-erbB2 (++++), P53 (+), E-cadherin (++++), CyclinD1 (++++), Ki67 10%. Postoperative diagnosis: left breast cancer pT1micpN0cM0 (2003 version of AJCC breast cancer TNM stage). Postoperative adjuvant endocrine therapy (oral letrozole 2.5 mg , once daily).
2. Discussion
The NCCN (2007 edition) clinical practice guidelines for breast cancer have clear definitions and treatment guidelines for ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), but the diagnosis and treatment principles for patients with DCIS with interstitial microinfiltration still need to be However, the diagnosis and treatment principles for patients with DCIS with interstitial microinfiltration need to be understood in depth. In this paper, the clinical symptoms and signs of the two patients were very similar, but the treatment plan and prognosis were obviously different, in which a detailed and accurate pathological diagnosis was essential. The pathology of case 1 was reported as DCIS, but there were many focal infiltrating cancer tissues in the interstitial mammary gland, and necrosis was seen in the ducts, and the cancer tissues broke through the basement membrane with a diameter of 2 mm. The patient’s final pathological diagnosis was IDC according to the AJCC (2003 version) TNM staging of breast cancer; pT1apN2cM0. It was a stage II breast cancer with high risk of recurrence [>8 axillary lymph node metastases, C-erb B2(+)]. In accordance with the NCCN (2007 version) clinical practice guidelines for breast cancer, liver metastases were found 19 months postoperatively despite sequential T×4 adjuvant chemotherapy with CA×4 and adjuvant radiotherapy to the chest wall and supraclavicular region, and finally sequential endocrine therapy with aromatase inhibitors for the patient. Case 2 was pathologically reported as DCIS with scattered irregular single cancer cell infiltrations in few interstitium and invasion of interstitium <1 mm in diameter (Figure 3), although this patient also had interstitial infiltration, the interstitial infiltration was <1 mm, and the pathological diagnosis was typical ductal carcinoma in situ with microinvasion (ductal carcinoma in situ with microinvasion , DCIS-MI); and lymph node metastasis (C). The final pathological diagnosis was DCIS-MI, pT1micpN0cM0, according to the TNM staging of breast cancer in AJCC (2003 version). endocrine adjuvant therapy was given, and no recurrence or metastasis was observed at the 6-month postoperative review.
The following clinical questions remain for DCIS-MI: (1) How to define DCIS-MI? (2) How to choose the examination method? (3) What are the biological characteristics and prognosis? (4) How to choose local treatment? (5) How to choose systemic treatment?
A review of the relevant literature is summarized below.
2.1 Definition Breast cancer with microinfiltration refers to breast cancer cells breaking through the basement membrane into adjacent tissues, while the maximum diameter does not exceed 0.1 cm. In case of multifocal microinfiltration, the microinfiltrating foci with the largest diameter should be used as the basis for staging (rather than the sum of the diameters of each infiltrating point as the index), and the index of multifocal microinfiltration should be indicated.
2.2 Examination methods Ultrasound, mammography, MRI, fine-needle aspiration cytology biopsy, hollow-core needle aspiration biopsy, and surgical biopsy are commonly used in clinical practice. Mammography is usually considered to have the greatest diagnostic value in the non-invasive examination of breast cancer. In recent years, with the development of breast MRI, especially the new advances in MRI dynamic enhancement scanning technology, functional and metabolic imaging and molecular imaging, the sensitivity and specificity of breast MRI have been greatly improved. However, there is no test with higher sensitivity and specificity for the diagnosis of DCIS-MI.Leikola et al [1] retrospectively studied 20 patients with DCIS-MI and found that ultrasound-visible masses were risk factors predicting microinfiltration in patients with DCIS, whereas palpable masses on physical examination and mass shape and size seen on mammography did not indicate microinfiltration.Velden et al [ 2] found that the specificity of MRI for the diagnosis of DCIS-MI was 83% (10/12); Dillon et al [3] found 93 cases of DCIS in 895 breast cancer patients with hollow-core needle biopsy, while 13 (14%) of them had postoperative pathology of DCIS-MI, with the presence of a high false-negative rate. Therefore, as far as the available data are concerned, there is no specific examination method for DCIS-MI. MRI and hollow-core needle aspiration are not highly specific for patients with DCIS-MI, and there is a possibility of overestimation or underestimation of the lesion, which needs to be further studied; while ultrasound examination has certain diagnostic significance for DCIS-MI and has the advantages of being inexpensive and easy to carry out, and should be recommended for application.
2.3 Biological characteristics and prognosis Most scholars believe that DCIS-MI is a breast cancer between DCIS and IDC, and its biological characteristics and malignancy are also between the two.Mascarel [4] reported 1248 patients, including 722 cases of DCIS, 243 cases of DCIS-MI and 283 cases of IDC, and analyzed the clinical and pathological characteristics and prognosis of the three groups. The clinical, pathological characteristics and prognosis of the three groups were analyzed, and it was concluded that the biological behavior and prognosis of DCIS-MI were between DCIS and IDC: the pathological type, tumor cell grading and tumor size of DCIS-MI patients were similar to DCIS, and the lymph node metastasis was between the two, with a better overall prognosis but lower disease-free survival and overall survival than DCIS.
2.4 Local treatment Total mastectomy is a curative procedure for DCIS. With the success of breast-conserving surgery for IDC, there has been a shift in recent years to explore the possibility of breast-conserving surgery for DCIS. The NSABP B-06 trial of 76 patients with DCIS with a mean follow-up of 83 months found that the ipsilateral breast cancer recurrence rate was significantly higher in patients after breast-conserving surgery alone compared with those in the breast-conserving plus radiotherapy group (43% vs. 7%. The EORTC counted 10,853 DCIS patients, 1010 of whom underwent breast-conserving surgery, and the difference in local recurrence rates between patients who received postoperative radiotherapy and those who did not was significant (15% vs. 25%, P ≤ 0.0001), but failed to significantly reduce invasive recurrence [6]. The former had significantly higher rates of invasive and non-invasive recurrence than the latter (16.8% vs. 7.7%, P=0.00001; 14.6% vs. 8%, P=0.001), but the 4-year overall survival rates were not significantly different between the two (86% vs. 87%, P=0.80), when DCIS patients undergoing breast-conserving surgery were randomized to the breast-conserving group alone and the postoperative radiotherapy group with 10.7 years of follow-up [7-9]. There is a lack of large prospective clinical trials on the choice of surgical modality for DCIS-MI; Rosner et al [10] and Solin et al [11] performed total mastectomy and breast-conserving surgery in patients with DCIS-MI, respectively, with no significant difference in overall survival rates (Table 1). Therefore, breast-conserving surgery with adjuvant radiotherapy can be chosen based on the analysis of the biology of the specific patient, while total mastectomy with one-stage molding is also a feasible option.
Table 1 Choice of surgical approach for patients with DCIS-MI
Investigator Rosner Solin
Number of cases 33 39
Surgical modality Total mastectomy Breast-conserving surgery
Follow-up time (months) 57 55
Local recurrence rate (%) 0 23
Overall survival rate (%) 100 97
Most scholars believe that sentinel lymph node biopsy is beneficial: Sakr et al [12] concluded that sentinel lymph node biopsy is effective in evaluating axillary micrometastases in patients with DCIS and DCIS-MI; Zavaqno et al [13] found that sentinel lymph node biopsy detected axillary lymph node metastases in 9.4% of patients with DCIS-MI. Parra et al [14] found that for high-grade Parra et al [14] found that for patients with high grade DCIS and sieve carcinoma, DCIS with necrosis, and DCIS-MI applying sentinel lymph node biopsy, 19.6% (10/51) of patients were found to have positive lymph nodes.
2.5 Systemic treatment The NSABP B-24 trial of 1804 female patients with DCIS randomized to the tamoxifen and placebo groups after lumpectomy and radiotherapy with a mean follow-up of 74 months found that the incidence of breast cancer-related events was significantly lower in the tamoxifen group than in the placebo group (8.2 vs. 13.4%, P=0.0009), indicating that tamoxifen is beneficial for ER-positive female patients with DCIS is beneficial, which is consistent with the IDC patient data [15]. Therefore, the choice of tamoxifen for ER(+) DCIS-MI patients is reasonable. However, there is a lack of evidence-based medical evidence for the choice of adjuvant chemotherapy, and whether patients with low risk of recurrence can be treated with reference to DCIS, while patients with intermediate or high risk of recurrence can be treated with reference to IDC deserves further study and discussion.
In summary, DCIS-MI has been clearly defined, but there is a lack of specific preoperative screening methods, and its biological behavior is between DCIS and IDC, which may have a poor prognosis for a small number of patients. It is recommended to choose breast-conserving surgery with adjuvant radiotherapy or total mastectomy with one-stage molding, together with an anterior lymph node biopsy to aid in axillary evaluation, and postoperative adjuvant therapy can be selected based on accurate, rigorous pathological findings, taking into account the patient’s specific situation. In this paper, Case 2 was a 70-year-old patient with pathological stage pT1micpN0cM0, and modified radical surgery with adjuvant endocrine therapy was the appropriate treatment.
3. Conclusion
With the advancement of clinical diagnostic tools, the incidence of DCIS has gradually increased. At present, the treatment modality of DCIS has been clearly defined, breast-conserving surgery with adjuvant radiotherapy or total breast excision with one-stage molding should be chosen, and postoperative endocrine therapy should be selected according to the hormone receptor status.DCIS-MI is a breast cancer between DCIS and IDC, and accurate pathological diagnosis is the key to treatment.The diameter of cancer cells that break through the basement membrane into adjacent tissues should be determined by pathology for DCIS-MI. If the diameter is >1mm, it is IDC and should be treated according to the corresponding stage.
References
[1]Leikola J,Päivi Heikkilä,Martti Pamilo et al, Predicting invasion in patients with DCIS in the preoperative percutaneous biopsy [J]. Acta Oncol, 2007, 46(6):798-802.
[2] Arjan P, Schouten van der Velden, Carla Boetes, et al. The value of magnetic resonance imaging in diagnosis and size assessment of in situ and small invasive breast carcinoma[J]. Am J Surg,2006,192(2) :172-178.
[3]Mary F,Dillon, Enda W, et al. Predictors of invasive disease in breast cancer when core biopsy demonstrates DCIS only[J]. J Surg Oncol,2006,93(7):559-563.
[4]Isabelle de Mascarel,Gae¨ tan MacGrogan,Simone Mathoulin-Pe´ lissier,et al. Breast Ductal Carcinoma In Situ with Microinvasion[J]. Cancer, 2002, 94(8):2134C2142.
[5] Fisher ER, Leeming R, Anderson S, et al. Conservative management of intraductal carcinoma (DCIS) of the breast [J]. J Surg Oncol, 1991, 47(3):139-147.
[6] Bijker N, Meijnen PH, Bogaerts J, et al. Radiotherapy in breast-conserving treatment for ductal carcinoma in situ (DCIS): ten-year results of European organization for research and treatment of cancer (EORTC) randomized trial 10853 [abstract] [J]. Breast Cancer Res Treat, 2005, 94(Suppl 1):A7.
[7] Fisher B, Costantino J, Redmond C, , et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer [ J]. N Engl J Med, 1993, 328(22):1581-1586.
[8] Fisher B, Dignam J, Wolmark N, et al. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17[J]. J Clin Oncol, 1998,16(2):441-452.
[9] Fisher B, Land S, Mamounas E, et al. Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience[J]. Semin Oncol,2001,28(4):400-418.
[10] Rosner D, Lane WW, Penetrante R. Duct carcinoma in situ with microinvasion: a curable entity using surgery alone without need for adjuvant therapy [J ]. Cancer, 1991, 67(6):1498-1503.
[11] Solin LJ, Fowble B, Yeh IT , et al, Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation[ J]. Int J Radiat Oncol Biol Phys,1992,(23): 961C968.
[12] Rita Sakr, E. Barranger, M. Antoine, et al. Ductal Carcinoma In Situ:Value of Sentinel Lymph Node Biopsy. J of Surg Oncol 2006;94:426C430
[13] Giorgio Zavagno, Valentina Belardinelli, Renato Marconato, et al. Sentinel lymph node metastasis from mammary ductal carcinoma in situ with microinvasion[J]. Breast, 2007,16(2):146-151.
[14] van la Parra RF, Ernst MF, Barneveld PC,et al. The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast. the breast.[abstract] [J]. Eur J Surg Oncol,2007 Sep 10:1016.
[15] Fisher B, Dignam J, Wolmark N,et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial[J]. Lancet, 1999 ,353(9169):1993-2000.