During the first couple years of onset, symptoms can partially or completely disappear for days to months, but return in other parts of the body. Causes
Current medical science does not precisely describe the causes of dystonia, however genetic and environmental factors may play a large role. Misfiring of neurons in the sensorimotor cortex, a thin layer of neural tissue that covers the brain, is thought to cause contractions. This misfiring may result from impaired inhibitory mechanisms during muscle contraction. When the brain tells a given muscle to contract, it simultaneously silences muscles that would oppose the intended movement. It appears that dystonia interferes with the brains ability to inhibit those surrounding muscles, leading to loss of selectivity.The sensorimotor cortex is organized as discrete "maps" of the human body. Under normal conditions, each body part (such as individual fingers) occupies a distinct area on these cortical maps. In dystonia, these maps lose their distinct borders and overlap occurs. Exploration of this initially involved over-training particular finger movements in non-human primates, which resulted in the development of focal hand dystonia. Examination of the primary somatosensory cortex in the trained animals showed grossly distorted representations of the maps pertaining to the fingers when compared to the untrained animals. Additionally, these maps in the dystonic animals had lost the distinct borders that were noted in the untrained animals. Imaging studies in humans with focal dystonia have confirmed this finding.
Participants were randomized to receive neoadjuvant chemotherapy with concurrent administration of either the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase or intravenous pertuzumab and intravenous trastuzumab during the neoadjuvant and adjuvant therapies.The primary endpoint of FeDeriCa was non-inferiority of cycle 7 pertuzumab serum trough concentration comparing the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase to intravenous pertuzumab. Secondary endpoints included cycle 7 trastuzumab serum trough concentration, pathological complete response (pCR), and safety. The fixed-dose combination showed non-inferior pertuzumab and trastuzumab serum trough concentrations compared to intravenous pertuzumab and trastuzumab. The pCR rate was 59.7% (95% CI: 53.3, 65.8) in the pertuzumab/trastuzumab/hyaluronidase arm and 59.5% (95% CI: 53.2, 65.6) in the intravenous pertuzumab and intravenous trastuzumab arm. The safety profile of the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase is comparable to intravenous pertuzumab and trastuzumab, except for increased administration-related reactions.The FDA granted approval of Phesgo to Genentech Inc.

Society and culture
Legal status
On 12 November 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Phesgo, intended for the treatment of early and metastatic breast cancer. The applicant for this medicinal product is Roche Registration GmbH. Phesgo was approved for medical use in the European Union in December 2020. References
Further reading
"AusPAR: Pertuzumab/trastuzumab". Therapeutic Goods Administration (TGA). 11 October 2021. External links
"Pertuzumab". Drug Information Portal. U.S. National Library of Medicine. "Trastuzumab". Drug Information Portal. U.S. National Library of Medicine. "Hyaluronidase". Drug Information Portal. U.S. National Library of Medicine.