Adjuvant Radiation Therapy for Male Breast Cancer—A Rare Indication?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patient and Tumor Characteristics
2.2. Oncological Outcome
2.3. Toxicity
3. Discussion
4. Materials and Methods
4.1. Patients and Treatment
4.2. Statistical Analysis
4.3. Ethical Approval
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
BCS: | Breast-Conserving Surgery |
BRCA2: | Breast Cancer 2 Gene |
CI: | Confidence Interval |
DCIS: | Ductal Carcinoma In Situ |
DFS: | Disease-Free Survival |
EBRT: | External Beam Radiation Therapy |
FBC: | Female Breast Cancer |
HER2: | Human Epidermal Growth Factor Receptor 2 |
HER2/neu: | Human Epidermal Growth Factor Receptor 2 |
IMRT: | Intensity-Modulated Radiotherapy |
LC: | Local Control |
LRC: | Locoregional Control |
MBC: | Male Breast Cancer |
OS: | Overall survival |
SD | Standard Deviation |
References
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 2020, 70, 7–30. [Google Scholar] [CrossRef]
- Giordano, S.H.; Cohen, D.S.; Buzdar, A.U.; Perkins, G.; Hortobagyi, G.N. Breast carcinoma in men: A population-based study. Cancer 2004, 101, 7–51. [Google Scholar] [CrossRef]
- Sanguinetti, A.; Polistena, A.; Lucchini, R.; Monacelli, M.; Galasse, S.; Avenia, S.; Triola, R.; Bugiantella, W.; Cirocchi, R.; Rondelli, F.; et al. Male breast cancer, clinical presentation, diagnosis and treatment: Twenty years of experience in our breast unit. Int. J. Surg. Case. Rep. 2016, 20S, 8–11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Losurdo, A.; Rota, S.; Gullo, G.; Masci, G.; Torrisi, R.; Bottai, G.; Zuradelli, M.; Gatzemeier, W.; Santoro, A. Controversies in clinicopathological characteristics and treatment strategies of male breast cancer: A review of the literature. Crit. Rev. Oncol. Hematol. 2017, 113, 283–291. [Google Scholar] [CrossRef] [PubMed]
- Fentiman, I.S.; Fourquet, A.; Hortobagyi, G.N. Male breast cancer. Lancet 2006, 367, 595–604. [Google Scholar] [CrossRef]
- Ventham, N.T.; Hussien, M.I. Male breast cancer is rare: An initial presentation may be as an abscess. BMJ Case Rep. 2010, 2010. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Antoniou, A.; Pharoah, P.D.; Narod, S.; Risch, H.A.; Eyfjord, J.E.; Hopper, J.L.; Loman, N.; Olsson, H.; Johannsson, O.; Borg, A.; et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: A combined analysis of 22 studies. Am. J. Hum. Genet. 2003, 72, 1117–1130. [Google Scholar] [CrossRef] [Green Version]
- Cardoso, F.; Bartlett, J.M.S.; Slaets, L.; van Deurzen, C.H.M.; van Leeuwen-Stok, E.; Porter, P.; Linderholm, B.; Hedenfalk, I.; Schroder, C.; Martens, J.; et al. Characterization of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG international male breast cancer program. Ann. Oncol. 2018, 29, 405–417. [Google Scholar] [CrossRef]
- Leitlinienprogramm Onkologie. Deutsche Krebsgesellschaft (DKG), S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms. Available online: http://www.leitlinienprogramm-onkologie.de/leitlinien/mammakarzinom/ (accessed on 14 November 2020).
- Ruddy, K.J.; Winer, E.P. Male breast cancer: Risk factors, biology, diagnosis, treatment, and survivorship. Ann. Oncol. 2013, 24, 1434–1443. [Google Scholar] [CrossRef]
- Yu, E.; Suzuki, H.; Younus, J.; Elfiki, T.; Stitt, L.; Yau, G.; Vujovic, O.; Perera, F.; Lock, M.; Tai, P. The impact of post-mastectomy radiation therapy on male breast cancer patients--a case series. Int. J. Radiat. Oncol. Biol. Phys. 2012, 82, 696–700. [Google Scholar] [CrossRef]
- Jardel, P.; Vignot, S.; Cutuli, B.; Creisson, A.; Vass, S.; Barranger, E.; Thariat, J. Should adjuvant radiation therapy be systematically proposed for male breast cancer? Syst. Review. Anticancer Res. 2018, 38, 23–31. [Google Scholar]
- Eggemann, H.; Ignatov, A.; Stabenow, R.; von Minckwitz, G.; Rohl, F.W.; Hass, P.; Costa, S.D. Male breast cancer: 20-year survival data for post-mastectomy radiotherapy. Breast Care 2013, 8, 270–275. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abrams, M.J.; Koffer, P.P.; Wazer, D.E.; Hepel, J.T. Postmastectomy radiation therapy is associated with improved survival in node-positive male breast cancer: A population analysis. Int. J. Radiat. Oncol. Biol. Phys. 2017, 98, 384–391. [Google Scholar] [CrossRef] [PubMed]
- Iorfida, M.; Bagnardi, V.; Rotmensz, N.; Munzone, E.; Bonanni, B.; Viale, G.; Pruneri, G.; Mazza, M.; Cardillo, A.; Veronesi, P.; et al. Outcome of male breast cancer: A matched single-institution series. Clin. Breast Cancer 2014, 14, 371–377. [Google Scholar] [CrossRef]
- Foerster, R.; Foerster, F.G.; Wulff, V.; Schubotz, B.; Baaske, D.; Wolfgarten, M.; Kuhn, W.C.; Rudlowski, C. Matched-pair analysis of patients with female and male breast cancer: A comparative analysis. BMC Cancer 2011, 11, 335. [Google Scholar] [CrossRef] [Green Version]
- Kiluk, J.V.; Lee, M.C.; Park, C.K.; Meade, T.; Minton, S.; Harris, E.; Kim, J.; Laronga, C. Male breast cancer: Management and follow-up recommendations. Breast J. 2011, 17, 503–509. [Google Scholar] [CrossRef]
- Sroufe, R.L.; Schwartz, D.; Rineer, J.; Choi, K.; Rotman, M.; Schreiber, D. A population-based study of the impact of post-mastectomy radiation on survival for male breast cancer. J. Radiat. Oncol. 2012, 1, 337–345. [Google Scholar] [CrossRef] [Green Version]
- Rushton, M.; Kwong, A.; Visram, H.; Graham, N.; Petrcich, W.; Dent, S. Treatment outcomes for male breast cancer: A single-centre retrospective case-control study. Curr. Oncol. 2014, 21, e400–e407. [Google Scholar] [CrossRef] [Green Version]
- Zabel, A.; Milker-Zabel, S.; Zuna, I.; Wannenmacher, M.; Debus, J. External beam radiotherapy in the treatment of male breast carcinoma: Patterns of failure in a single institute experience. Tumori 2005, 91, 151–155. [Google Scholar] [CrossRef]
- Darby, G.S.; McGale, P.; Correa, C.; Taylor, C.; Arriagada, R.; Clarke, M.; Cutter, D.; Davies, C.; Ewertz, M.; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG); et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 2011, 378, 1707–1716. [Google Scholar]
- McGale, P.; Taylor, C.; Correa, C.; Cutter, D.; Duane, F.; Ewertz, M.; Gray, R.; Mannu, G.; Peto, R.; Whelan, T.; et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014, 383, 2127–2135. [Google Scholar] [PubMed]
- Liedtke, C.; Thill, M.; Jackisch, C.; Thomssen, C.; Muller, V.; Janni, W.; on behalf of the AGO Breast Committee. AGO recommendations for the diagnosis and treatment of patients with early breast cancer: Update 2017. Breast Care 2017, 12, 172–183. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anderson, W.F.; Jatoi, I.; Tse, J.; Rosenberg, P.S. Male breast cancer: A population-based comparison with female breast cancer. J. Clin. Oncol. 2010, 28, 232–239. [Google Scholar] [CrossRef]
- Yadav, S.; Karam, D.; Bin Riaz, I.; Xie, H.; Durani, U.; Duma, N.; Giridhar, K.V.; Hieken, T.J.; Boughey, J.C.; Mutter, R.W.; et al. Male breast cancer in the United States: Treatment patterns and prognostic factors in the 21st century. Cancer 2020, 126, 26–36. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Madden, N.A.; Macdonald, O.K.; Call, J.A.; Schomas, D.A.; Lee, C.M.; Patel, S. Radiotherapy and male breast cancer: A population-based registry analysis. Am. J. Clin. Oncol. 2016, 39, 458–462. [Google Scholar] [CrossRef] [PubMed]
- Fields, E.C.; DeWitt, P.; Fisher, C.M.; Rabinovitch, R. Management of male breast cancer in the United States: A surveillance, epidemiology and end results analysis. Int. J. Radiat. Oncol. Biol. Phys. 2013, 87, 747–752. [Google Scholar] [CrossRef]
- Nahleh, Z.A.; Srikantiah, R.; Safa, M.; Jazieh, A.R.; Muhleman, A.; Komrokji, R. Male breast cancer in the veterans affairs population: A comparative analysis. Cancer 2007, 109, 1471–1477. [Google Scholar] [CrossRef]
- Leone, J.P.; Leone, J.; Zwenger, O.; Iturbe, J.; Leone, B.A.; Vallejo, C.T. Locoregional treatment and overall survival of men with T1a,b,cN0M0 breast cancer: A population-based study. Eur. J. Cancer 2017, 7–14. [Google Scholar] [CrossRef]
- Scott-Conner, C.E.; Jochimsen, P.R.; Menck, H.R.; Winchester, D.J. An analysis of male and female breast cancer treatment and survival among demographically identical pairs of patients. Surgery 1999, 126, 775–780; discussion 780–781. [Google Scholar] [CrossRef]
- Chakravarthy, A.; Kim, C.R. Post-mastectomy radiation in male breast cancer. Radiother. Oncol. 2002, 65, 99–103. [Google Scholar] [CrossRef]
- Donegan, W.L.; Redlich, P.N.; Lang, P.J.; Gall, M.T. Carcinoma of the breast in males: A multiinstitutional survey. Cancer 1998, 83, 498–509. [Google Scholar] [CrossRef]
- Macdonald, G.; Paltiel, C.; Olivotto, I.A.; Tyldesley, S. A comparative analysis of radiotherapy use and patient outcome in males and females with breast cancer. Ann. Oncol. 2005, 16, 1442–1448. [Google Scholar] [CrossRef] [PubMed]
- Nielsen, H.M.; Overgaard, M.; Grau, C.; Jensen, A.R.; Overgaard, J.; Danish Breast Cancer Cooperative Group. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: Long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J. Clin. Oncol. 2006, 24, 2268–2275. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rogowski, P.; Schonecker, S.; Pazos, M.; Reitz, D.; Braun, M.; Polcher, M.; Hanusch, C.; Wuerstlein, R.; Harbeck, N.; Mahner, S.; et al. Pattern of care of adjuvant radiotherapy in male breast cancer patients in clinical practice: An observational study. Strahlenther Onkol. 2019, 195, 289–296. [Google Scholar] [CrossRef] [PubMed]
- Rolf, D.; Elsayad, K.; Meheissen, M.A.M.; Elkerm, Y.; Opitz, C.; Radke, I.; Bremer, A.; Hulskamp, A.; Elsaka, R.; Ismail, H.M.; et al. Impact of Adjuvant Radiation Therapy in Patients With Male Breast Cancer: A Multicenter International Analysis. Adv. Radiat. Oncol. 2020, 5, 345–349. [Google Scholar] [CrossRef]
- Potter, R.; Gnant, M.; Kwasny, W.; Tausch, C.; Handl-Zeller, L.; Pakisch, B.; Taucher, S.; Hammer, J.; Luschin-Ebengreuth, G.; Schmid, M.; et al. Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 2007, 68, 334–340. [Google Scholar] [CrossRef]
- Fyles, A.W.; McCready, D.R.; Manchul, L.A.; Trudeau, M.E.; Merante, P.; Pintilie, M.; Weir, L.M.; Olivotto, I.A. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N. Engl. J. Med. 2004, 351, 963–970. [Google Scholar] [CrossRef]
- Muller, A.C.; Gani, C.; Rehm, H.M.; Eckert, F.; Bamberg, M.; Hehr, T.; Weinmann, M. Are there biologic differences between male and female breast cancer explaining inferior outcome of men despite equal stage and treatment?! Strahlenther Onkol. 2012, 188, 782–787. [Google Scholar] [CrossRef]
- Hong, J.H.; Ha, K.S.; Jung, Y.H.; Won, H.S.; An, H.J.; Lee, G.J.; Kang, D.; Park, J.C.; Park, S.; Byun, J.H.; et al. Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years. Cancer Res. Treat. 2016, 48, 1389–1398. [Google Scholar] [CrossRef]
- Francis, S.R.; Frandsen, J.; Kokeny, K.E.; Gaffney, D.K.; Poppe, M.M. Outcomes and utilization of postmastectomy radiotherapy for T3N0 breast cancers. Breast 2017, 32, 156–161. [Google Scholar] [CrossRef]
Characteristics | Patients (Total: 41) | % | |
---|---|---|---|
Patient Characteristics | |||
Age at diagnosis | Median (years) | 67 | |
Range (years) | 36–83 | ||
BMI | <30 | 23 | 56.1 |
30–34.9 | 5 | 12.2 | |
>34.9 | 3 | 7.3 | |
unknown | 10 | 24.4 | |
Performance status (Karnofsky) | Median (%) | 90 | |
Range (%) | 60–100 | ||
Tumor Characteristics | |||
Histology | DCIS | 2 | 4.9 |
Invasive ductal | 34 | 82.9 | |
Invasive lobular | 3 | 7.3 | |
Other | 2 | 4.9 | |
Side | Right breast | 19 | 46.3 |
Left breast | 22 | 53.7 | |
Location | Lower inner | 1 | 2.4 |
Lower outer | 0 | 0 | |
Upper inner | 0 | 0 | |
Upper outer | 6 | 14.7 | |
Central | 34 | 82.9 | |
Tumor size | Median (cm) | 2.6 | |
Range (cm) | 0.6–5.5 | ||
R status | R0 | 39 | 95.2 |
R1 | 1 | 2.4 | |
R2 | 1 | 2.4 | |
pT status | pTis | 2 | 4.9 |
pT1a | 1 | 2.4 | |
pT1b | 1 | 2.4 | |
pT1c | 8 | 19.5 | |
pT2 | 17 | 41.6 | |
pT3 | 1 | 2.4 | |
pT4a | 1 | 2.4 | |
pT4b | 9 | 22.0 | |
pT4c | 1 | 2.4 | |
pN status | pN0 | 16 | 39.0 |
pN1 | 13 | 31.7 | |
pN2 | 7 | 17.1 | |
pN3 | 5 | 12.2 | |
Lymphangiosis | Yes | 19 | 46.3 |
No | 13 | 31.7 | |
Unknown | 9 | 22.0 | |
Tumor grade | G1 | 2 | 4.9 |
G2 | 27 | 65.9 | |
G3 | 12 | 29.2 | |
Estrogen receptor status | Positive | 35 | 85.3 |
Negative | 2 | 4.9 | |
Not tested | 4 | 9.8 | |
Progesterone receptor status | Positive | 33 | 80.4 |
Negative | 4 | 9.8 | |
Not tested | 4 | 9.8 | |
HER2/neu status | Positive | 2 | 4.9 |
Negative | 29 | 70.7 | |
Not tested | 10 | 24.4 | |
Ki-67 status | Median (%) | 19.0 | |
Range (%) | 5–50 | ||
Treatment Characteristics | |||
Surgical procedure | Mastectomy | 38 | 92.7 |
BCS | 3 | 7.3 | |
Axillary dissection | Yes | 35 | 85.4 |
No | 6 | 14.6 | |
Sentinel lymph node extirpation | Yes | 7 | 17.1 |
No | 34 | 82.9 | |
No. of resected lymph nodes | Median | 13 | |
Range | 1–41 | ||
Chemotherapy | None | 23 | 56.1 |
Neoadjuvant only | 0 | 0 | |
Adjuvant only | 17 | 41.5 | |
Neoadjuvant and adjuvant | 1 | 2.4 | |
Endocrine therapy | Yes | 33 | 80.5 |
No | 8 | 19.5 | |
Radiation technique | IMRT | 8 | 19.5 |
3D-CRT | 25 | 61.0 | |
2D-CRT | 8 | 19.5 | |
Nodal irradiation | Yes | 23 | 56.1 |
No | 18 | 43.9 | |
Irradiation of IMA | 8 | 19.5 | |
Irradiation of SCN | 19 | 46.3 | |
Irradiation of ALN | 7 | 17.1 | |
Treatment dose | Median (Gy) | 50.0 | |
Range (Gy) | 40.05–50.4 | ||
Single fraction dose | Median (Gy) | 1.9 | |
Range (Gy) | 1.8–2.67 | ||
Boost | Yes | 24 | 58.5 |
No | 17 | 41.5 | |
Boost dose | Median (Gy) | 10 | |
Range (Gy) | 10–16 |
Toxicity | Patients (Total: 41) | % | |
---|---|---|---|
Acute Toxicity | 38 | 92.7 | |
Pain | Any grade | 3 | 7.3 |
CTCAE grade I | 3 | 7.3 | |
CTCAE grade ≥ II | 0 | 0 | |
Fatigue | Any grade | 9 | 21.9 |
CTCAE grade I | 8 | 19.5 | |
CTCAE grade II | 1 | 2.4 | |
CTCAE grade III | 0 | 0 | |
Erythema and dry desquamation | Any grade | 37 | 90.2 |
CTCAE grade I | 24 | 58.5 | |
CTCAE grade II | 13 | 31.7 | |
CTCAE grade III | 0 | 0 | |
Late Side Effects | 23 | 56.1 | |
Hyperpigmentation | CTCAE grade I | 16 | 39.0 |
CTCAE grade ≥ II | 0 | 0 | |
Lymphedema | CTCAE grade I | 10 | 24.4 |
CTCAE grade ≥ II | 0 | 0 | |
Fibrosis | Any grade | 0 | 0 |
Telangiectasia | CTCAE grade I | 1 | 2.4 |
CTCAE grade ≥ II | 0 | 0 | |
Restriction of arm movement | CTCAE grade I | 4 | 9.8 |
CTCAE grade ≥ II | 0 | 0 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Forster, T.; Köhler, C.; El Shafie, R.; Weykamp, F.; König, L.; Arians, N.; Adeberg, S.; Michel, L.; Smetanay, K.; Golatta, M.; et al. Adjuvant Radiation Therapy for Male Breast Cancer—A Rare Indication? Cancers 2020, 12, 3645. https://doi.org/10.3390/cancers12123645
Forster T, Köhler C, El Shafie R, Weykamp F, König L, Arians N, Adeberg S, Michel L, Smetanay K, Golatta M, et al. Adjuvant Radiation Therapy for Male Breast Cancer—A Rare Indication? Cancers. 2020; 12(12):3645. https://doi.org/10.3390/cancers12123645
Chicago/Turabian StyleForster, Tobias, Clara Köhler, Rami El Shafie, Fabian Weykamp, Laila König, Nathalie Arians, Sebastian Adeberg, Laura Michel, Katharina Smetanay, Michael Golatta, and et al. 2020. "Adjuvant Radiation Therapy for Male Breast Cancer—A Rare Indication?" Cancers 12, no. 12: 3645. https://doi.org/10.3390/cancers12123645