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Palpable Ductal Carcinoma in situ: A Paradox of Benign Mind with Malignant Action!
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(02): 244-246
DOI: DOI: 10.4103/ijmpo.ijmpo_88_20
Ductal carcinoma in situ (DCIS) accounts for 30% of the cancers detected through breast screening, while it is <5% in the symptomatic population, and microinvasion (DCIS-M) is found in 10%–14% of the palpable tumors with DCIS.[1] The most common presentation is a palpable mass often with nipple discharge.[2] [3] Current guidelines for the management of DCIS refer to screen detected DCIS. In this era of de-escalation of treatment for DCIS, we need to evaluate pDCIS as a distinct entity which is different from low-risk screen-detected lesions. There are no defined treatment guidelines for pDCIS or DCIS-M.
Evaluation for all women who present with a breast lump includes the triple test wherein a clinical evaluation, imaging with mammography with or without ultrasound and histopathological confirmation, is done. The role of MRI in evaluating DCIS is limited with low sensitivity ranging from 72% to 84%.[4] The management and extent of surgery are same as for early invasive cancers. The disease must be mapped accurately on imaging. However, with noncalcific DCIS, there is a higher risk of margin positivity which must be kept in mind. No prospective randomized trial has compared mastectomy to breast-conserving surgery in women with DCIS. A meta-analysis of studies published up to 1998 reported local recurrence rates of 22.5% (95% confidence interval [CI] =16.9%–28.2%), 8.9% (95% CI = 6.8%–11%), and 1.4% (95% CI = 0.7%–2.1%) for lumpectomy alone, lumpectomy with radiation, and mastectomy, respectively.[5] The lack of a difference in survival between the two approaches has led to a decline in the use of mastectomy, which is now offered to patients with multicentric disease, large lesions, other contraindications to breast conservation, or a personal preference for mastectomy, as is with invasive cancers.
pDCIS has a 10%–14% risk of harboring an invasive component. It is essential to differentiate microinvasive DCIS from multiple foci of invasive ductal carcinoma (IDC) in a background of DCIS with extensive intraductal component (EIC). There are, however, multiple definitions of DCIS with microinvasion. As per the American Joint Committee on Cancer (AJCC), the size of only the largest focus should be used to classify the microinvasion when there is more than one focus. Although multiple foci suggest higher tumor volume, the AJCC advises not to use the sum of the size of all the individual foci, and that multiple foci of microinvasion should be noted.[6] In addition to the AJCC classification, de Mascarel et al.[7] defined two distinct types of DCIS-M and evaluated their clinical significance. Type 1 has a single site of infiltration beyond the basement membrane, behaves similar to DCIS, and should be treated as such. Type 2, harboring numerous clusters of microinvasion, has a worse prognosis and needs to be treated more aggressively. Thus, identifying the microinvasion and number of foci is essential to planning further management in the cases of pDCIS. Various studies have evaluated factors that predict the presence of microinvasion wherein large tumor, comedo-type architecture, and estrogen receptor negativity were found to be independent predictors of microinvasion (all P < 0.001).[8]
The pathologist’s role is critical in defining whether this is a case of pDCIS or DCIS-M Type 1 or Type 2. Thus, sampling the entire specimen and mapping entire tumor is critical to ensure that pDCIS has no invasion. For tumor mapping, the grossly visible lesion is “bread-loafed” and sliced serially at distance of 1 cm. Each slice is then cut into square sections which are labeled consecutively. This allows us to construct the entire DCIS microscopically and define size of DCIS as well as invasive tumor if any, for example, if two consecutive sections show invasive carcinoma and each sectioned is 3 mm, then 3 mm × 2 mm = 6 mm size. Furthermore, if available, radiographically guided grossing is recommended in cases of DCIS.[9]
For screen-detected DCIS, National comprehensive cancer network recommends the role of sentinel lymph node biopsy, only in cases undergoing a modified radical mastectomy. The incidence of axillary lymph node metastases with DCIS is only 1.4%, while with DCIS-M, it is higher at 5.1%.[10] Possible indications for axillary lymph node dissection are the suspicion of microinvasion, such as the presence of a clinically palpable node or palpable comedo-type DCIS. However due to the underestimation of invasion in biopsies of pDCIS, we advocate lymphatic mapping using sentinel lymph node biopsy or axillary sampling at the time of surgery, with both modified radical mastectomy and breast-conserving procedure.
Studies evaluating types of DCIS-M have suggested that patients with DCIS and DCIS-M Type 1 had better metastasis-free and overall survival than patients with DCIS-M Type 2, and patients with DCIS-M Type 2 had better metastasis-free and overall survival than patients with IDC–DCIS.[7] However, the role of adjuvant therapy in pDCIS and DCIS-M is still not clear.
Management of triple-negative and Her 2-positive disease pDCIS or DCIS-M is more controversial than that of hormone receptor (HR) positive. Tamoxifen is the standard adjuvant therapy for HR-positive cases, recommended for 5 years.[11] The risk of subsequent invasive ipsilateral breast cancer was found to be reduced by tamoxifen versus placebo in DCIS.[11] In terms of efficacy and safety, tamoxifen and aromatase inhibitor were found comparable (91% vs. 93%). However, with varying spectrum of side effects, anastrozole was associated with musculoskeletal pain, hypercholesterolemia, and strokes, while tamoxifen was associated with muscle spasm, deep-vein thrombosis, and gynecological cancers.[12]
Notably, this entity is uncommon is Western world, and hence, no clear treatment guidelines about adjuvant chemotherapy exist. However, there is a case for adjuvant chemotherapy in pDCIS or DCIS-M. We conducted a retrospective audit of cases treated from 2005 to 2016, treated at our institution, wherein we identified 784 cases of with DCIS, DCIS-M, and early invasive cancer with EIC at our center. Among these, 740/784 (94.4%) presented with palpable breast lumps, of which 14.4% had Tis and 43.5% of DCIS had microinvasion. On follow–up, distant recurrences were noted in 5 (4.4%) patients with Tis, 3 (3.4%) with T1 mic, 21 (9.5%) with T1, and 63 (17.3%) with T2, (P = 0.00). Limited use of adjuvant chemotherapy in Tis and T1 mic may have contributed to the high distant recurrences in that group (unpublished data).
We recommend the use of adjuvant chemotherapy, especially in high-risk cases with palpable Type 2 DCIS-M (multiple foci of invasion in a background of DCIS), especially in cases with Her2/neu-positive microinvasive foci. This entity, however, being rare and with lack of high-quality guidelines merits individualized case-based discussions in multidisciplinary tumor boards.
We conclude that DCIS presenting in palpable lesions poses a clinical dilemma for the use of adjuvant therapy, especially in cases with DCIS-M. We thus need to reconsider grossing techniques and the role of adjuvant chemotherapy in treating pDCIS. It seems prudent to categorize DCIS-M as a small invasive tumor with a generally favorable outcome. However, at times, it can behave like “the one with benign mind but malignant action” and merits individualized precision care.
Publication History
Received: 05 March 2020
Accepted: 28 April 2020
Article published online:
23 May 2021
© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Ductal carcinoma in situ (DCIS) accounts for 30% of the cancers detected through breast screening, while it is <5% in the symptomatic population, and microinvasion (DCIS-M) is found in 10%–14% of the palpable tumors with DCIS.[1] The most common presentation is a palpable mass often with nipple discharge.[2] [3] Current guidelines for the management of DCIS refer to screen detected DCIS. In this era of de-escalation of treatment for DCIS, we need to evaluate pDCIS as a distinct entity which is different from low-risk screen-detected lesions. There are no defined treatment guidelines for pDCIS or DCIS-M.
Evaluation for all women who present with a breast lump includes the triple test wherein a clinical evaluation, imaging with mammography with or without ultrasound and histopathological confirmation, is done. The role of MRI in evaluating DCIS is limited with low sensitivity ranging from 72% to 84%.[4] The management and extent of surgery are same as for early invasive cancers. The disease must be mapped accurately on imaging. However, with noncalcific DCIS, there is a higher risk of margin positivity which must be kept in mind. No prospective randomized trial has compared mastectomy to breast-conserving surgery in women with DCIS. A meta-analysis of studies published up to 1998 reported local recurrence rates of 22.5% (95% confidence interval [CI] =16.9%–28.2%), 8.9% (95% CI = 6.8%–11%), and 1.4% (95% CI = 0.7%–2.1%) for lumpectomy alone, lumpectomy with radiation, and mastectomy, respectively.[5] The lack of a difference in survival between the two approaches has led to a decline in the use of mastectomy, which is now offered to patients with multicentric disease, large lesions, other contraindications to breast conservation, or a personal preference for mastectomy, as is with invasive cancers.
pDCIS has a 10%–14% risk of harboring an invasive component. It is essential to differentiate microinvasive DCIS from multiple foci of invasive ductal carcinoma (IDC) in a background of DCIS with extensive intraductal component (EIC). There are, however, multiple definitions of DCIS with microinvasion. As per the American Joint Committee on Cancer (AJCC), the size of only the largest focus should be used to classify the microinvasion when there is more than one focus. Although multiple foci suggest higher tumor volume, the AJCC advises not to use the sum of the size of all the individual foci, and that multiple foci of microinvasion should be noted.[6] In addition to the AJCC classification, de Mascarel et al.[7] defined two distinct types of DCIS-M and evaluated their clinical significance. Type 1 has a single site of infiltration beyond the basement membrane, behaves similar to DCIS, and should be treated as such. Type 2, harboring numerous clusters of microinvasion, has a worse prognosis and needs to be treated more aggressively. Thus, identifying the microinvasion and number of foci is essential to planning further management in the cases of pDCIS. Various studies have evaluated factors that predict the presence of microinvasion wherein large tumor, comedo-type architecture, and estrogen receptor negativity were found to be independent predictors of microinvasion (all P < 0.001).[8]
The pathologist’s role is critical in defining whether this is a case of pDCIS or DCIS-M Type 1 or Type 2. Thus, sampling the entire specimen and mapping entire tumor is critical to ensure that pDCIS has no invasion. For tumor mapping, the grossly visible lesion is “bread-loafed” and sliced serially at distance of 1 cm. Each slice is then cut into square sections which are labeled consecutively. This allows us to construct the entire DCIS microscopically and define size of DCIS as well as invasive tumor if any, for example, if two consecutive sections show invasive carcinoma and each sectioned is 3 mm, then 3 mm × 2 mm = 6 mm size. Furthermore, if available, radiographically guided grossing is recommended in cases of DCIS.[9]
For screen-detected DCIS, National comprehensive cancer network recommends the role of sentinel lymph node biopsy, only in cases undergoing a modified radical mastectomy. The incidence of axillary lymph node metastases with DCIS is only 1.4%, while with DCIS-M, it is higher at 5.1%.[10] Possible indications for axillary lymph node dissection are the suspicion of microinvasion, such as the presence of a clinically palpable node or palpable comedo-type DCIS. However due to the underestimation of invasion in biopsies of pDCIS, we advocate lymphatic mapping using sentinel lymph node biopsy or axillary sampling at the time of surgery, with both modified radical mastectomy and breast-conserving procedure.
Studies evaluating types of DCIS-M have suggested that patients with DCIS and DCIS-M Type 1 had better metastasis-free and overall survival than patients with DCIS-M Type 2, and patients with DCIS-M Type 2 had better metastasis-free and overall survival than patients with IDC–DCIS.[7] However, the role of adjuvant therapy in pDCIS and DCIS-M is still not clear.
Management of triple-negative and Her 2-positive disease pDCIS or DCIS-M is more controversial than that of hormone receptor (HR) positive. Tamoxifen is the standard adjuvant therapy for HR-positive cases, recommended for 5 years.[11] The risk of subsequent invasive ipsilateral breast cancer was found to be reduced by tamoxifen versus placebo in DCIS.[11] In terms of efficacy and safety, tamoxifen and aromatase inhibitor were found comparable (91% vs. 93%). However, with varying spectrum of side effects, anastrozole was associated with musculoskeletal pain, hypercholesterolemia, and strokes, while tamoxifen was associated with muscle spasm, deep-vein thrombosis, and gynecological cancers.[12]
Notably, this entity is uncommon is Western world, and hence, no clear treatment guidelines about adjuvant chemotherapy exist. However, there is a case for adjuvant chemotherapy in pDCIS or DCIS-M. We conducted a retrospective audit of cases treated from 2005 to 2016, treated at our institution, wherein we identified 784 cases of with DCIS, DCIS-M, and early invasive cancer with EIC at our center. Among these, 740/784 (94.4%) presented with palpable breast lumps, of which 14.4% had Tis and 43.5% of DCIS had microinvasion. On follow–up, distant recurrences were noted in 5 (4.4%) patients with Tis, 3 (3.4%) with T1 mic, 21 (9.5%) with T1, and 63 (17.3%) with T2, (P = 0.00). Limited use of adjuvant chemotherapy in Tis and T1 mic may have contributed to the high distant recurrences in that group (unpublished data).
We recommend the use of adjuvant chemotherapy, especially in high-risk cases with palpable Type 2 DCIS-M (multiple foci of invasion in a background of DCIS), especially in cases with Her2/neu-positive microinvasive foci. This entity, however, being rare and with lack of high-quality guidelines merits individualized case-based discussions in multidisciplinary tumor boards.
We conclude that DCIS presenting in palpable lesions poses a clinical dilemma for the use of adjuvant therapy, especially in cases with DCIS-M. We thus need to reconsider grossing techniques and the role of adjuvant chemotherapy in treating pDCIS. It seems prudent to categorize DCIS-M as a small invasive tumor with a generally favorable outcome. However, at times, it can behave like “the one with benign mind but malignant action” and merits individualized precision care.
References
- Tabár L, Vitak B, Chen HH, Duffy SW, Yen MF, Chiang CF. et al. The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long-term follow-up. Radiol Clin North Am 2000; 38: 625-51
- Rosner D, Bedwani RN, Vana J, Baker HW, Murphy GP. Noninvasive breast carcinoma: Results of a national survey by the American College of Surgeons. Ann Surg 1980; 192: 139-47
- Rajan SS, Verma R, Shaaban AM, Sharma N, Dall B, Lansdown M. Palpable ductal carcinoma in situ: Analysis of radiological and histological features of a large series with 5-year follow-up. Clin Breast Cancer 2013; 13: 486-91
- Itakura K, Lessing J, Sakata T, Heinzerling A, Vriens E, Wisner D. et al. The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ. Clin Breast Cancer 2011; 11: 33-8
- Boyages J, Delaney G, Taylor R. Predictors of local recurrence after treatment of ductal carcinoma in situ: A meta-analysis. Cancer 1999; 85: 616-28
- Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. editors AJCC cancer staging manual. 7th ed. France: Springer; 2010. Available from: http://www.springer.com/medicine/surgery/book/978-0-387-88440-0. [Last accessed on 2020 May 18].
- de Mascarel I, MacGrogan G, Mathoulin-Pélissier S, Soubeyran I, Picot V, Coindre JM. Breast ductal carcinoma in situ with microinvasion: A definition supported by a long-term study of 1248 serially sectioned ductal carcinomas. Cancer 2002; 94: 2134-42
- Kim M, Kim HJ, Chung YR, Kang E, Kim EK, Kim SH. et al. Microinvasive carcinoma versus ductal carcinoma in situ: A comparison of clinicopathological features and clinical outcomes. J Breast Cancer 2018; 21: 197-205
- Shet T, Desai SB, Patil A. Grossing of surgical oncology specimens. In: A Practical Guide towards Complete Pathology Reporting. Mumbai: Tata Memorial Hospital; 2011
- Leonard GD, Swain SM. Ductal carcinoma in situ, complexities and challenges. J Natl Cancer Inst 2004; 96: 906-20
- Fisher ER, Dignam J, Tan-Chiu E, Costantino J, Fisher B, Paik S. et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: Intraductal carcinoma. Cancer 1999; 86: 429-38
- Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S. et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): An international, double-blind, randomised placebo-controlled trial. Lancet 2014; 383: 1041-8
Address for correspondence
Publication History
Received: 05 March 2020
Accepted: 28 April 2020
Article published online:
23 May 2021
© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
- 1 Tabár L, Vitak B, Chen HH, Duffy SW, Yen MF, Chiang CF. et al. The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long-term follow-up. Radiol Clin North Am 2000; 38: 625-51
- 2 Rosner D, Bedwani RN, Vana J, Baker HW, Murphy GP. Noninvasive breast carcinoma: Results of a national survey by the American College of Surgeons. Ann Surg 1980; 192: 139-47
- 3 Rajan SS, Verma R, Shaaban AM, Sharma N, Dall B, Lansdown M. Palpable ductal carcinoma in situ: Analysis of radiological and histological features of a large series with 5-year follow-up. Clin Breast Cancer 2013; 13: 486-91
- 4 Itakura K, Lessing J, Sakata T, Heinzerling A, Vriens E, Wisner D. et al. The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ. Clin Breast Cancer 2011; 11: 33-8
- 5 Boyages J, Delaney G, Taylor R. Predictors of local recurrence after treatment of ductal carcinoma in situ: A meta-analysis. Cancer 1999; 85: 616-28
- 6 Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. editors AJCC cancer staging manual. 7th ed. France: Springer; 2010. Available from: http://www.springer.com/medicine/surgery/book/978-0-387-88440-0. [Last accessed on 2020 May 18].
- 7 de Mascarel I, MacGrogan G, Mathoulin-Pélissier S, Soubeyran I, Picot V, Coindre JM. Breast ductal carcinoma in situ with microinvasion: A definition supported by a long-term study of 1248 serially sectioned ductal carcinomas. Cancer 2002; 94: 2134-42
- 8 Kim M, Kim HJ, Chung YR, Kang E, Kim EK, Kim SH. et al. Microinvasive carcinoma versus ductal carcinoma in situ: A comparison of clinicopathological features and clinical outcomes. J Breast Cancer 2018; 21: 197-205
- 9 Shet T, Desai SB, Patil A. Grossing of surgical oncology specimens. In: A Practical Guide towards Complete Pathology Reporting. Mumbai: Tata Memorial Hospital; 2011
- 10 Leonard GD, Swain SM. Ductal carcinoma in situ, complexities and challenges. J Natl Cancer Inst 2004; 96: 906-20
- 11 Fisher ER, Dignam J, Tan-Chiu E, Costantino J, Fisher B, Paik S. et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: Intraductal carcinoma. Cancer 1999; 86: 429-38
- 12 Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S. et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): An international, double-blind, randomised placebo-controlled trial. Lancet 2014; 383: 1041-8